No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Abstract
Humans have enjoyed forest environments for ages because of the quiet atmosphere, beautiful scenery, mild climate, and fresh, clean air. In the present study, we found that visiting forest parks, but not a city, enhanced human natural killer (NK) activity, increased anti-cancer proteins, such as perforin, granzymes A and B, and granulysin in NK cells, and reduced the level of stress hormones in both male and female subjects. Moreover, this effect lasted for more than 30 days after the trips, suggesting that visiting a forest park once a month would enable individuals to maintain a higher level of NK activity. Phytoncides released from trees and the decreased production of stress hormones may partially contribute to the increased NK activity. Because NK cells can kill tumor cells by releasing anti-cancer proteins, and visiting forest parks increases NK activity and the amount of anti-cancer proteins; therefore, the above findings suggest that visiting forest parks may have a preventive effect on cancer generation and progression.
... First, consistent with the ''hygiene hypothesis,'' contact with microbial and other antigens in natural settings during particular developmental windows may modify (improve) immune function over the lifespan (Hanski et al. 2012, Kondrashova et al. 2013, Nicolaou et al. 2005, Rook 2013, Ruokolainen et al. 2015, Stiemsma et al. 2015, perhaps operating through effects on the microbiome (Lee and Mazmanian 2010). Second, short-term exposure to natural substances (such as phytoncides from trees) have been associated with improved natural killer (NK) cell activity (Li 2010, Li and Kawada 2011, Li et al. 2008a, Li et al. 2008b, Li et al. 2006. NK cells play important protective roles against cancer, viral infections, and inflammatory cytokines that have been implicated in diabetes, cardiovascular disease, depression, and other negative health outcomes (Cesari et al. 2003, Dowlati et al. 2010, Orange and Ballas 2006, Wellen and Hotamisligil 2005. ...
... Stress recovery and immune function mechanisms may not be distinct because of reciprocal relationships between these two physiologic systems (Irwin andCole 2011, Nusslock and. Fantuzzi (2013) also found that adiponectin levels in the body increase while in nature and improved landscapes (Li and Kawada 2011), which helps protect against atherosclerosis, acute urinary tract infections, infectious diseases of the intestinal canal, and upper respiratory tract infections. ...
... It also can help with circulatory and heart disease risks (Maas et al. 2009). Walking in nature also increases serum levels of adipo-nectin (Li and Kawada 2011) and regular walks could potentially protect against obesity, type 2 diabetes, hypertension, and coronary heart disease (Song et al. 2017). ...
This paper focused on providing evidence from the literature regarding the physiological health benefits associated with plants, thereby influencing the physiological, psychological, and cognitive well-being constructs affecting quality of life. These benefits are segmented and discussed using the following categories: better sleep, increased birthweights, decreased diabetes, decreased ocular discomfort, enhanced immunity, improved circadian functioning, improved rehabilitation, decreased cardiovascular and respiratory disease, decreased mortality, improved digestion, decreased allergies, increased physical activity, and improved cognitive development. This research should be strategically incorporated into both industry-wide and firm-specific marketing messages that highlight the quality of life value proposition in order to maintain the industry's sense of value and relevance to residential landscape consumers of the future. These findings also present evidence that municipal leaders and policymakers can use in justifying green infrastructure-related funding decisions, as well as grounds for the construction industry using biophilic design principles in ensuring the built environment offers opportunities for green space interactions. The green industry can play a pivotal role not only in providing plants of high quality for these applications but educating stakeholders regarding the benefits discussed herein.
Index words: benefits of plants, emotional health, mental health
... Potential confounding variables for this study include demographic information, such as age group (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44), 45-54, 55-64, and >65 years), gender (male or female), socioeconomic status (SES), such as insurance amount, occupational type (governmental employee and teachers, soldiers, service industries, agriculture workers, fishing and animal husbandry, non-governmental organizations, and others), and subjects' comorbidities (hypertension [ICD-9-CM codes = 401-405] and hyperlipidemia [ICD-9-CM code = 272]). Contextual socioeconomic circumstances are controlled and adjusted, for example, by county-level income information (scaled from 0-625, 625-1250, 1250-1875 and >1875 in USD/year) from the Taiwanese National Statistics and township urbanization levels (scaled from level 1: Urban core area; level 2: Downtown; level 3: Emerging town; level 4: Traditional industry area; level 5: Low development town; level 6: Aging society town; level 7: Rural area). ...
... Previous studies have demonstrated that forest bathing trips affected human immune function, leading to an increase in natural killer (NK) activity via increasing the levels of intracellular granulysin and performance in and the number of NK cells [25][26][27]. Thus, it was likely exposure to surrounding greenness might decrease the risk of developing T2DM through modulating immune function. In addition, Cho et al. have reported that the beneficial effects of forest bathing on human health might be through terpenes, the largest class of naturally occurring organic compounds, which have the effect of antiinflammatory, anti-cancer, or neuroprotective activities [28]. ...
This study determines whether surrounding greenness is associated with the incidence of type 2 diabetes Mellitus (T2DM) in Taiwan. A retrospective cohort study determines the relationship between surrounding greenness and the incidence of T2DM during the study period of 2001–2012 using data from the National Health Insurance Research Database. The satellite-derived normalized difference vegetation index (NDVI) from the global MODIS database in the NASA Earth Observing System is used to assess greenness. Cox proportional hazard models are used to determine the relationship between exposure to surrounding greenness and the incidence of T2DM, with adjustment for potential confounders. A total of 429,504 subjects, including 40,479 subjects who developed T2DM, were identified during the study period. There is an inverse relationship between exposure to surrounding greenness and the incidence of T2DM after adjustment for individual-level covariates, comorbidities, and the region-level covariates (adjusted HR = 0.81, 95% CI: 0.79–0.82). For the general population of Taiwan, greater exposure to surrounding greenness is associated with a lower incidence of T2DM.
... 4 Also, a few studies reported that natural killer (NK) cells are involved in immunologic mechanisms of forest environment through antiinflammatory properties and promoting immune function. [5][6][7] Nonetheless exposure to forest through walking, recreation, and forest bathing has been linked to positive effects on health, most previous studies have focused on limited clinical effects. 4 We thus hypothesized that a short-term exposure to forest environment would have not only clinical improvement but also immunologic effects on chronic allergic diseases. ...
... A few previous studies reported enhanced immune functions, as evidenced by increases in NK cell activity in patients who visit a forest environment. 5,6 Exposure to beneficial chemicals (i.e., phytoncides) released from a forest is often cited as a scientific basis for the positive effects of forest environment on human health. Moreover, the levels of airborne mold and PM 10 in the accommodations within forest were lower than those of children's homes. ...
Asthma and atopic dermatitis are common allergic diseases, and their prevalence has increased in urban children. Recently, it is becoming understood that forest environment has favorable health effects in patients with chronic diseases. To investigate favorable clinical and immunologic effects of forest, we examined changes in clinical symptoms, indirect airway inflammatory marker, and serum chemokines before and after a short-term forest trip. The forest trips were performed with 21 children with asthma and 27 children with atopic dermatitis. All participating children were living in air polluted urban inner-city. We measured spirometry and fractional exhaled nitric oxide (FeNO) in children with asthma and measured scoring atopic dermatitis (SCORAD) index and Thymus and Activation-Regulated Chemokine (TARC)/CCL17 and Macrophage-Derived Chemokine (MDC)/CCL22 levels in children with atopic dermatitis before and after the forest trip. Indoor air pollutants such as indoor mold, particulate matter 10 (PM10) and total volatile organic compounds (TVOCs) of each child's home and the accommodations within forest were measured. A significant increase in forced vital capacity (FVC) and a significant decrease in FeNO were observed after the forest trip in children with asthma. SCORAD indices and MDC/CCL22 levels were significantly decreased after the forest trip in children with atopic dermatitis. Airborne mold and PM10 levels in indoor were significantly lower in the forest accommodations than those of children's homes; however, TVOC levels were not different between the two measured sites. Short-term exposure to forest environment may have clinical and immunological effects in children with allergic diseases who were living in the urban community.
... In 2005, my research team conducted the first Shinrin-yoku study in Iiyama, Nagano prefecture in Japan and the terms of Shinrin-yoku and Forest Bathing in English were first named and defined by author in this study [1]. Shinrin-yoku is also a short leisurely visit to a forest field, which is similar in effect to natural aromatherapy, for the purpose of relaxation and the breathing in of volatile substances called phytoncides (wood essential oils) derived from plants (trees), such as alpha-pinene and limonene [1,[8][9][10]. Because forests occupy 67% of the land in Japan, Shinrin-yoku is easily accessible [11]. ...
Humans have enjoyed forest environments for ages because of the quiet atmosphere, beautiful scenery, mild climate, pleasant aromas, and fresh, clean air. In Japan, since 2004, serial studies have been conducted to investigate the effects of forest environments (Forest bathing/Shinrin-yoku) on human health. My research team has established a new medical science called Forest Medicine. The Forest Medicine is a new interdisciplinary science, belonging to the categories of alternative medicine, environmental medicine and preventive medicine, which studies the effects of forest environments (Forest bathing/Shinrin-yoku) on human health. It has been reported that Forest bathing/Shinrin-yoku has the following beneficial effects on human health:
1 Shinrin-yoku increases human natural killer (NK) activity, the number of NK cells, and the intracellular levels of anti-cancer proteins, suggesting a preventive effect on cancers.
2 Shinrin-yoku reduces blood pressure and heart rate showing preventive effect on hypertension and heart diseases.
3 Shinrin-yoku reduces stress hormones, such as urinary adrenaline and noradrenaline and salivary/serum cortisol contributing to stress management.
4 Shinrin-yoku increases the activity of parasympathetic nerves and reduces the activity of sympathetic nerves to stabilize the balance of autonomic nervous system.
5 Shinrin-yoku improve sleep.
6 Shinrin-yoku increases the levels of serum adiponectin and dehydroepiandrosterone sulfate.
7 In the Profile of Mood States (POMS) test, Shinrin-yoku reduces the scores for anxiety, depression, anger, fatigue, and confusion, and increases the score for vigor, showing preventive effects on depression.
8 Shinrin-yoku may apply to rehabilitation medicine
9 Shinrin-yoku in city parks also has benefits on human health.
10 Shinrin-yoku may have preventive effect on COVID-19 by boosting immune function and by reducing mental stress.
Taken together, these findings suggest that Shinrin-yoku may have potential preventive effects on non-communicable diseases.
... Stress resilience increases in people who visit a forest multiple times. The phytoncide that is released by trees reduces stress hormones and increases immunity by activating NK cells [13,15,69]. Therefore, in this study, it can be concluded that the stress of forest users and the perceived restorativeness are negatively correlated; in other words, stress is reduced and perceived restorativeness is increased. ...
Even though the COVID-19 pandemic has discouraged travel and people’s movements, the number of visitors to forests near cities which are easily accessible by private vehicle is increasing in Korea. This study aims to investigate the relationship between stress, perceived restorativeness, forest recreation motivation, and the mental well-being of forest users. A survey of forest users was conducted at three recreational forests near Seoul in the summer of 2020. A total of 1196 forest users (613 males and 583 females) participated in the study. As a result of the data analysis, it was found that stress had a negative correlation with perceived restorativeness, forest recreation motivation, and mental well-being; perceived restorativeness had a positive correlation with mental well-being, and forest recreation motivation had a positive correlation with mental well-being. For the relationship between stress and mental well-being, the fitness index that was mediated by the perceived restorativeness and the forest recreation motivation found that the model was statistically suitable. Through this study, a research model was derived that, if the stress of forest users is reduced, direct or indirect effects on perceived restorativeness, forest recreation motivation, and mental well-being are increased. Further, a multi-group analysis found that the effect of perceived restorativeness and forest recreation motivation on the mental well-being of the male group was higher than the effect on the female group. Using this research model to find ways to promote health in forests can be utilized for forest management or forest healing.
... Perhaps one of the most striking potential features of contact with nature, and sharing some commonality with other 'lifestyle' factors, are the seemingly pleiotropic beneficial health effects it may have on general health (Cox et al., 2017), including but not limited to improved birth outcomes (Dzhambov et al., 2014;Twohig-Bennett and Jones, 2018), asthma and allergies (Cavaleiro Rufo et al., 2021), improved immune functioning (Li et al., 2008;Li and Kawada, 2011;Hall and Knuth, 2019), diabetes (Brown et al., 2016;Thiering et al., 2016;Tsai et al., 2021), lowering blood pressure (Shanahan et al., 2016), reduction in pain perception acutely (Lechtzin et al., 2010) and chronically (Wells et al., 2019), improving postoperative recovery (Park and Mattson, 2009) and reduced mortality (James et al., 2016;Crouse et al., 2017). Furthermore, there is evidence to suggest beneficial effects on a number of possible mechanisms of action Frontiers in Psychology | www.frontiersin.org ...
There is growing interest in nature-based interventions (NBI) to improve human health and wellbeing. An important nascent area is exploring the potential of outdoor therapies to treat and prevent common mental health problems like depression. In this conceptual analysis on the nature–depression nexus, we distil some of the main issues for consideration when NBIs for depression are being developed. We argue that understanding the mechanisms, or ‘active ingredients’ in NBIs is crucial to understand what works and for whom. Successfully identifying modifiable mediating intervention targets will pave the way for interventions with increased efficacy. We highlight a non-exhaustive list of five clinically relevant putative, candidate mechanisms which may underly the beneficial effects of NBIs on depression: stress, rumination, mindfulness, sleep and exercise. We also make the case that when developing NBIs it is important to not neglect young people, explore personalised approaches and focus on both treatment and prevention approaches. To achieve these aims methodologically rigorous programmes of clinical research are needed that include well-powered and controlled experimental designs including randomised controlled trials, qualitative research, longitudinal studies and large prospective cohorts.
... High UV exposure and low humidity could be additional critical factors to explain the reductions in asthma severity in the high mountain climate 49 . It has been shown that Recreational winter exercise at moderately cold temperatures reduces allergic airway inflammation measured as FeNO, nasal eosinophilic cell count, and induces sustainable improvements in allergic symptoms 50 . Moreover, a study revealed higher human natural killer (NK) activity, increased anti-cancer proteins such as perforin, granzymes A and B, and granulysin Novelty in Biomedicine 2022, 1, 76-88 in natural killer (NK) cells, and lower stress hormone levels both men and women who visited forest parks but not cities. ...
... 9 Additional theorized mechanisms include a boost in one's immune system from contact with microbes or exposure to certain natural substances such as phytoncides from trees. 10 Preschool children recruited to participate in a 10-week structured nature-related program displayed a significant reduction in perceived stress, particularly in the frequency of anger, and an abundance of fecal serotonin, demonstrating the impact exposure to nature has on psychosocial behavior and mood. 11 There is also a lot of research surrounding gratitude and its role in improving psychological health and reducing negative emotions. ...
While minimally susceptible to COVID-19, the pediatric population is most vulnerable to the psychosocial repercussions of this pandemic as they have faced setbacks and struggle to maintain normality in nearly every aspect of their lives. Duration of quarantine, fear of infection, limited social interaction, and more have had a significant positive correlation with poorer mental health, PTSD, anxiety, and anger. Young people have been burdened mentally and emotionally by the stressors of the COVID-19 pandemic. They have been thrown off their regular course and expected to quickly adapt to new parameters, restrictions, and limitations. The pandemic has undoubtedly had a significant impact on shaping their childhood trajectory as it has interrupted regular milestones and life checkoffs. In an aim to heal and ameliorate COVID-related anxiety, stress, and negative mental health consequences, utilization of appropriate coping strategies is encouraged and particularly important for disadvantaged groups who report multiple obstacles to pursuing treatment for mental health issues.
... The primary explanation for this lack of scripting is that it remains unclear exactly which aspects of nature are responsible for the beneficial outcomes. Although it has been shown that, for example, visual stimulation [92,93], olfactory consumption of volatile organic compounds [94,95] and physical contact with wood [96] all promote positive outcomes, the precise mechanisms remain uncertain. The difficulty of identifying the relevant mechanisms lies in the fact that 'Nature' is tremendously complex and involves multi-species interaction. ...
Heavy goods vehicle (HGV) driving is recognised as a highly hazardous occupation due to the long periods of sedentary behaviour, low levels of physical activity and unhealthy food options when working. These risk factors combine with shift work and concomitant irregular sleep patterns to increase the prevalence of fatigue. Fatigue is closely linked with stress and, subsequently, poor physiological and psychological health. In parallel, a wealth of evidence has demonstrated the health and wellbeing benefits of spending time in nature. Here, we sought to examine whether spending time in nature was associated with lower levels of fatigue, anxiety and depression in HGV drivers. 89 long-distance drivers (98.9% male, mean ± SD age: 51.0 ± 9 years, body mass index: 29.8 ± 4.7 kg/m2) participating in a wider health promotion programme reported time spent in nature (during and before the Covid-19 pandemic) and symptoms of occupational fatigue, depression and anxiety. After controlling for covariates, truck drivers who visited nature at least once a week exhibited 16% less chronic fatigue prior to the pandemic, and 23% less chronic fatigue and 20% less acute fatigue during the pandemic. No significant differences were observed for either anxiety or depression. As fatigue has a range of physical and mental health sequelae, we propose that increased exposure to natural settings may make a valuable contribution to interventions to promote the health and wellbeing of this underserved group.
... The pathways to positive health effects may be via physical and social activity as well as improved air quality [23]. Improved immune functioning from contact with microbial or other antigens [21] or exposure to certain natural substances such as phytoncides from trees [24] may also function as a mechanism for associated health benefits. The most widely investigated psychological pathways are attention restoration and stress reduction, but other factors, such as emotion regulation and feelings of awe or mystery, may mediate positive health outcomes [20]. ...
Research has proven that both mindfulness training and exposure to nature have positive health effects. The purpose of this study was to systematically review quantitative studies of mindfulness interventions conducted in nature (nature-based mindfulness), and to analyze the effects through meta-analyses. Electronic searches revealed a total of 25 studies to be included, examining 2990 participants. Three analyses were conducted: Nature-based mindfulness interventions evaluated as open trials (k = 13), nature-based mindfulness compared with groups in non-active control conditions (k = 5), and nature-based mindfulness compared with similar interventions but without contact with nature (k = 7). The overall combined psychological, physiological, and interpersonal effects from pre- to post-intervention were statistically significant and of medium size (g = 0.54, p < 0.001). Moderation analyses showed that natural environments characterized as forests/wild nature obtained larger numerical effects than environments characterized as gardens/parks, as did informal mindfulness compared with formal mindfulness. The small number of studies included, as well as the heterogeneity and generally low quality of the studies, must be taken into consideration when the results are interpreted. PROSPERO registration number: CRD42017065639.
... When humans breathe phytoncides, our bodies boost the number and activity of natural killer (NK) cells, white blood cells that protect us from viruses and tumors. 28,29 Forest bathing increases NK activity and promotes the expression of more anti-cancer proteins. 30 In a study of over 100,000 women, even after controlling for age, race, smoking, and income, those who lived in the greenest settings had 12% lower risk of dying than those in the least green settings; the greatest benefits were for lung disease and cancer. ...
... This could lead to physiological relaxation and immune-function recovery through five-sense stimulation during forest therapy [1]. Several studies have shown that five-sense stimulation from forest therapy could improve anxiety and depression symptoms and stabilize the effects of autonomic dysfunction [22][23][24][25]. Second, forest oils, such as phytoncide, have several positive effects on physical and emotional health with respect to recovery from stressful conditions [18,19]. ...
The improvement of sleep quality in patients with cancer has a positive therapeutic effect on them. However, there are no specific treatment guidelines for treating sleep disturbance in cancer patients. We investigated the effect of forest therapy on the quality of sleep in patients with cancer. This study was conducted on nine patients (one male, eight female; mean age, 53.6 ± 5.8 years) with gastrointestinal tract cancer. All patients participated in forest therapy for six days. They underwent polysomnography (PSG) and answered questionnaires on sleep apnea (STOP BANG), subjective sleep quality (Pittsburgh Sleep Quality Index, PSQI), sleepiness (Stanford and Epworth Sleepiness Scales), and anxiety and depression (Hospital Anxiety and Depression Scale) to evaluate the quality of sleep before and after forest therapy. Sleep efficiency from the PSG results was shown to have increased from 79.6 ± 6.8% before forest therapy to 88.8 ± 4.9% after forest therapy (p = 0.027) in those patients, and total sleep time was also increased, from 367.2 ± 33.4 min to 398 ± 33.8 min (p = 0.020). There was no significant difference in the STOP BANG score, PSQI scores, daytime sleepiness based on the results of the Stanford and Epworth Sleepiness Scales, and depression and anxiety scores. Based on the results of this study, we suggest that forest therapy may be helpful in improving sleep quality in patients with gastrointestinal cancers.
... Second, children at nature preschools may be less likely to inhale airborne viruses, given the abundance of circulating fresh air outdoors (Pica & Bouvier, 2012). Third, proximity to trees could confer beneficial health effects, as there is evidence that tree emissions such as phytoncides enhance immune activity (Cho, Lim, Lee, Lee, Lee, & Lee, 2017;Li & Kawada, 2010;Li et al., 2009;Li et al., 2008). However, outdoor exposure may confer an increased risk of illness. ...
Nature preschools, where children spend the entire school day outdoors, are increasingly popular, but their health consequences have not been well researched. This study tested the hypothesis that nature preschools and conventional preschools differ in their illness and injury incidence, by comparing observed illness and injury occurrence in the two types of schools. For 14 weeks, teachers at five nature preschools and four conventional preschools in Seattle, Washington logged absences due to illness. Two nature preschools and three conventional preschools also logged injuries that occurred during the school day. There was no difference in illness incidence by preschool type, and no serious injuries were reported in either setting. Overall, the study found that nature preschools are a healthy and safe child-care model.
... First, consistent with the "hygiene hypothesis," contact with microbial and other antigens in natural settings during particular developmental windows may modify immune function over the lifespan (Hanski et al. 2012;Kondrashova et al. 2013;Nicolaou et al. 2005;Rook 2013;Ruokolainen et al. 2015;Stiemsma et al. 2015), perhaps operating through effects on the microbiome (Lee and Mazmanian 2010). Second, short-term exposures to some natural substances (such as phytoncides from trees) have been associated with improved natural killer (NK) cell activity (Li et al. 2006(Li et al. , 2008a(Li et al. , 2008b(Li et al. , 2010Li and Kawada 2011). Stress recovery and immune function mechanisms may not be distinct because of reciprocal relationships between these two physiologic systems (Irwin and Cole 2011;Nusslock and Miller 2016). ...
Background:
At a time of increasing disconnectedness from nature, scientific interest in the potential health benefits of nature contact has grown. Research in recent decades has yielded substantial evidence, but large gaps remain in our understanding.
Objectives:
We propose a research agenda on nature contact and health, identifying principal domains of research and key questions that, if answered, would provide the basis for evidence-based public health interventions.
Discussion:
We identify research questions in seven domains: a) mechanistic biomedical studies; b) exposure science; c) epidemiology of health benefits; d) diversity and equity considerations; e) technological nature; f) economic and policy studies; and g) implementation science.
Conclusions:
Nature contact may offer a range of human health benefits. Although much evidence is already available, much remains unknown. A robust research effort, guided by a focus on key unanswered questions, has the potential to yield high-impact, consequential public health insights. https://doi.org/10.1289/EHP1663.
... Under the stress of restraint, strokeprone, spontaneously hypertensive rats exposed to phytoncides showed lower blood pressure than those without such exposure [16], indicating that phytoncides may have anti-stress effects. Phytoncides increase natural killer cell activity [17,18]. This favorable effect on immune functioning may in turn have a favorable psychoneuroimmunological influence. ...
Background: Studies have shown that walking in forests can have a relaxation effect, but the participants only walked for about 15 minutes.
Methods and findings: The study adopted an open crossover design, in which 22 healthy male volunteers were randomly assigned to two groups. The first group walked the Kodo forest course first and the urban course second, while the second group completed the walks in the reverse order. The Kodo course was 4 km from the foot to the pass and back, and took around 2 hours. The participants walked the urban course at an exercise intensity equal to that of the Kodo course. We used both physiological and psychological measures to examine the relaxation effect of walking. Salivary amylase concentrations significantly increased from the start to the end of the urban course, and were significantly higher at the end of the urban course than at the end of the Kodo course. Saliva cortisol concentrations decreased from the start to the end of both courses, and were significantly lower at the end of the Kodo course than the urban course. Analysis of the Profile of Mood State data showed significant decreases in “Tension-Anxiety”, “Depression-Dejection depression”, “Anger-Hostility” and “Confusion” after walking both courses, and a significant decrease in “Vigor” after the urban course. Visual analog scores were significantly higher on the Kodo course, but decreased significantly on the urban course. The electrocardiogram analysis showed no noticeable change in the HF component time series for the urban course, although it tended to be higher on the Kodo course than the urban course. The LF/HF ratio was slightly higher for the urban course than for the Kodo course throughout.
Conclusions: The physiological and psychological measures indicate that walking for 2 hours in the forest is effective for relaxation.
... Negative air ions also interact with phytoncides released from trees which in turn can interact with microbes, altogether influencing the environmental atmosphere [14]. Phytoncides may also act directly on the innate immune system, as they have been shown to increase the level of natural killer cells [15]. ...
Background
The specific microclimate of alpine waterfalls with high levels of ionized water aerosols has been suggested to trigger beneficial immunological and psychological effects. In the present three-armed randomized controlled clinical study, we focused on effects on (i) immunological reagibility, on (ii) physiological stress responses, and on (iii) stress-related psychological parameters.
Methods
People with moderate to high stress levels (n = 65) spent an active sojourn with daily hiking tours in the National Park Hohe Tauern (Großkirchheim, Austria). Half of the group was exposed to water aerosol of an alpine waterfall for 1 h/day (first arm, n = 33), whereas the other half spent the same time at a distant site (second arm, n = 32). A third arm (control, n = 26) had no intervention (except vaccination) and stayed at home, maintaining their usual lifestyle. The effect of the interventions on the immune system was tested by oral vaccination with an approved cholera vaccine and measuring specific salivary IgA antibody titers. Lung function was determined by peak expiratory flow measurement. Electric skin conductance, heart rate, and adaption of respiration rate were assessed as physiological stress parameters. Psychological stress-related parameters were analyzed by questionnaires and scales.
Results
Compared to the control group, both intervention groups showed improvement of the lung function and of most physiological stress test parameters. Analysis of the mucosal immune response revealed a waterfall-specific beneficial effect with elevated IgA titers in the waterfall group. In line with these results, exposure to waterfall revealed an additional benefit concerning psychological parameters such as subjective stress perception (measured via visual analog scale), the Global Severity Index (GSI), and the Positive Symptom Total (PST).
Conclusions
Our study provides new data, which strongly support an “added value” of exposure to waterfall microclimate when combined with a therapeutic sojourn at high altitude including regular physical activity.
... While still requiring larger sample sizes and replication of existing work, studies involving shinrinyoku (now generally referred to in Japanese studies as simply "forest medicine" or "forest therapy") have grown in sophistication. Spending time in a forest environment has been linked with decreased cortisol, inflammatory cytokine (and chemokine) production, lowered blood pressure, improved heart rate variability, and elevations in natural killer cell activity [23][24][25][26][27][28][29]. ...
Recent advances in research concerning the public health value of natural environments have been remarkable. The growing interest in this topic (often housed under terms such as green and/or blue space) has been occurring in parallel with the microbiome revolution and an increased use of remote sensing technology in public health. In the context of biodiversity loss, rapid urbanization, and alarming rates of global non-communicable diseases (many associated with chronic, low-grade inflammation), discussions of natural vis-a-vis built environments are not merely fodder for intellectual curiosity. Here, we argue for increased interdisciplinary collaboration with the aim of better understanding the mechanisms—including aerobiological and epigenetic—that might help explain some of the noted positive health outcomes. It is our contention that some of these mechanisms are related to ecodiversity (i.e., the sum of biodiversity and geodiversity, including biotic and abiotic constituents). We also encourage researchers to more closely examine individual nature relatedness and how it might influence many outcomes that are at the interface of lifestyle habits and contact with ecodiversity.
... A variety of studies have shown that spending time walking or contemplating in a forest setting is associated with lower cortisol (a stress hormone), lower blood pressure and pulse rate, and increased heart rate variability (Li et al. 2008;Logan and Selhub 2012). Visits to forest settings have been shown to improve immune responses and the production of anti cancer proteins (Li and Kawada 2011). Individuals exposed to nature experience decreased recovery times post-illness or -operation and a decreased need for anal gesia compared with those with no nature exposure . ...
... Some previous reports have suggested that serum granulysin and lysozyme concentrations reflect the absolute numbers of NK cells and neutrophils, respectively (Ganz, 2004;Li & Kawada, 2012;Zhang et al., 2006), and thus enteric-coated LF supplementation may not always cause the overall number of neutrophils and NK cells to increase. Butcher et al. (2001) investigated the effect of ageing on neutrophil bactericidal responses by comparing neutrophil function in healthy, young persons to that of elderly persons and demonstrated that neutrophil CD16 expression was correlated with phagocytic capacity in the elderly subjects. ...
... Outdoor play, gardening, or any activity that might bring contact with soil, trees, and plant life will increase the opportunity for exposure to microbial diversity. If the activity is conducted in natural environments, it increases the likelihood that the individual will inhale natural phytoncides (aromatic chemicals secreted from trees and ornamental plants) that are associated with human stress reduction and immune system benefits [211,212]. These airborne phytoncides, found at higher levels in natural (vs. ...
Famed microbiologist René J. Dubos (1901–1982) was an early pioneer in the developmental origins of health and disease (DOHaD) construct. In the 1960s, he conducted groundbreaking research concerning the ways in which early-life experience with nutrition, microbiota, stress, and other environmental variables could influence later-life health outcomes. He recognized the co-evolutionary relationship between microbiota and the human host. Almost 2 decades before the hygiene hypothesis, he suggested that children in developed nations were becoming too sanitized (vs. our ancestral past) and that scientists should determine whether the childhood environment should be “dirtied up in a controlled manner.” He also argued that oft-celebrated growth chart increases via changes in the global food supply and dietary patterns should not be equated to quality of life and mental health. Here in the second part of our review, we reflect the words of Dubos off contemporary research findings in the areas of diet, the gut-brain-axis (microbiota and anxiety and depression) and microbial ecology. Finally, we argue, as Dubos did 40 years ago, that researchers should more closely examine the relevancy of silo-sequestered, reductionist findings in the larger picture of human quality of life. In the context of global climate change and the epidemiological transition, an allergy epidemic and psychosocial stress, our review suggests that discussions of natural environments, urbanization, biodiversity, microbiota, nutrition, and mental health, are often one in the same.
... Acute physiological markers can include pulse rate, blood pressure, skin conductance, salivary cortisol, temperature, and other factors which demonstrate nervous system arousal [123]; chronic physiological markers can include changes in urinary metabolites, immune defense and inflammatory markers, and other indicators in blood chemistry [124]; behavioral markers can include prosocial behavior [125] or self-regulation [126]; emotional markers can include self-rated evaluations of mood, including depression and anxiety; and cognitive markers include performance on work tasks, working memory capacity [127], capacity to pay attention, accuracy, efficiency, and reaction time [128][129][130][131]. ...
This paper summarizes the discussions from the Natural Environments Initiative meeting hosted by the Harvard School of Public Health’s Center for Global Health and the Environment and the Harvard Radcliffe Institute for
Advanced Studies in October 2013. It presents ongoing worldwide research on health benefits stemming from exposure to natural environments and design cues with particular attention applications in urban environments.
This meeting generated a Workshop statement forged by the participants that affirms the health benefits of nature and presents the need for additional collaborative, transdisciplinary to refine salutogenic planning and design practices.
Workshop participants represented disciplinary and professional perspectives from medicine, landscape architecture, public heath, and forestry science rooted in the cultural, ecological and political realities of a dozen countries and five continents. When framing the benefits of nature, they considered health outcomes including mental health disorders, obesity, Type 2 diabetes, metabolic disorders, allergies, cardiovascular disease, and more. Many environmental factors (including those related to physical activity, residential planning, environmental contamination and severe weather attributed to climate change) mediate these health outcomes at local, regional and global levels. This paper provides an illustrative review that captures many relevant studies discussed during the workshop. Although not exhaustive, our review indicates that the available evidence is applicable to various populations and ecological settings, and broadly supports the association of improved health outcomes with exposure to natural environments.
Full report available at: http://www.chgeharvard.org/sites/default/files/resources/Paper-NaturalEnvironmentsInitiative_0.pdf
... Acute physiological markers can include pulse rate, blood pressure, skin conductance, salivary cortisol, temperature, and other factors which demonstrate nervous system arousal [123]; chronic physiological markers can include changes in urinary metabolites, immune defense and inflammatory markers, and other indicators in blood chemistry [124]; behavioral markers can include prosocial behavior [125] or self-regulation [126]; emotional markers can include self-rated evaluations of mood, including depression and anxiety; and cognitive markers include performance on work tasks, working memory capacity [127], capacity to pay attention, accuracy, efficiency, and reaction time [128][129][130][131]. ...
This paper summarizes the discussions from the Natural Environments Initiative meeting hosted by the Center for Health and the Global Environment at the Harvard School of Public Health and the Harvard Radcliffe Institute for Advanced Studies in October 2013. It presents ongoing worldwide research on health benefits stemming from exposure to natural environments and design cues with particular attention applications in urban environments.
This meeting generated a Workshop statement forged by the participants that affirms the health benefits of nature and presents the need for additional collaborative, transdisciplinary to refine salutogenic planning and design practices. Workshop participants represented disciplinary and professional perspectives from medicine, psychology, landscape architecture, public heath, and forestry science rooted in the cultural, ecological and political realities of a dozen countries and five continents. When framing the benefits of nature, they considered health outcomes including mental health disorders, obesity, Type 2 diabetes, metabolic disorders, allergies, cardiovascular disease, and more. Many environmental factors (including those related to physical activity, residential planning, environmental contamination and severe weather attributed to climate change) mediate these health outcomes at local, regional and global levels. This paper provides an illustrative review that captures many relevant studies discussed during the workshop. Although not exhaustive, our review indicates that the available evidence is applicable to various populations and ecological settings, and broadly supports the association of improved health outcomes with exposure to natural environments.
http://www.chgeharvard.org/sites/default/files/resources/NaturalEnvironmentsInitiative.pdf http://www.chgeharvard.org/resource/natural-environments-initiative-illustrative-review-and-workshop-statement http://www.chgeharvard.org/NEI_Paper
... Several other studies focused on the immune system (e.g. Kondo et al. 2011, Li and Kawada 2011a. Li et al. (2006), for example, found that essential oils in wood, so-called phytoncides, have an effect on human natural killer cells (NK), that were incubated with phytoncides in vitro. ...
Chronic stress and little physical activity play an increasing role in dominant civilization diseases. The positive contribution of nature to health has been examined in a multitude of studies. The ambition of this study is to review the present state of international research on exposure to forests and its specific effects on human health, particularly stress-reducing effects. The review focusses on research in Asia and German-speaking countries (GSC) in Europe, distinguishing between forest benefits for physical and mental well-being. Considering the objective of the EU Forest Action Plan (FAP) to contribute to quality of life by improving the social dimensions of forests, it also examines and compares the forest strategies and programmes of GSC. With regard to plan implementation at national levels, attention is drawn to preventive health care aspects. The results are discussed and challenges, especially for forestry in GSC, are deduced.
Spanish
El estrés crónico y la escasa actividad física desempeñan un papel creciente en las enfermedades dominantes de la civilización. La contribución positiva de la naturaleza a la salud ha sido examinada en multitud de estudios. La meta de este trabajo es revisar el estado actual de la investigación internacional sobre la exposición a los bosques y sus efectos específicos sobre la salud humana, en particular los efectos de reducción del estrés. La revisión se centra en investigaciones en Asia y en países de habla alemana (GSC, por sus siglas en inglés) en Europa, distinguiendo entre los beneficios de los bosques para el bienestar físico y mental. Teniendo en cuenta el objetivo del Plan de Acción de la Unión Europea en Defensa de los Bosques de contribuir a la calidad de vida mediante la mejora de las dimensiones sociales de los bosques, se examinan y comparan asimismo las estrategias y programas forestales de los GSC en Europa. En cuanto a la planificación de la implementación a nivel nacional, se hace una llamada de atención sobre los aspectos de la asistencia sanitaria preventiva. Se discuten los resultados y deducen los desafíos, especialmente para el sector forestal en los GSC.
French
Le stress chronique et la carence d'activités physiques jouent un rôle prépondérant dans les maladies dominantes de notre civilisation. La contribution positive de la nature à la santé a été examinée dans une multitude d'études. Cette étude a pour ambition de présenter l'état actuel de la recherche internationale sur l'exposition aux forêts, sur ses effets spécifiques sur la santé humaine, et sur ses effets pour réduire le stress en particulier. L'étude se concentre sur la recherche en Asie et dans les pays germanophones (GSC) en Europe, en distinguant les bénéfices des forêts pour le bien-être physique et le bien-être mental. Tour en considérant l'objectif du Plan d'action des forêts de l'Union Européènne (FAP) visant à contribuer à la qualité de vie en améliorant les dimensions sociales des forêts, il examine et compare également les stratégies forestières et les programmes des GSC. Dans le but de prévoir une mise en oeuvre au niveaux nationaux, notre attention est attirée sur les aspects des soins préventifs. Les résultats sont analysés et les défis en sont déduits, en particulier pour la foresterie dans les GSC.
... Previous studies have shown stress relaxing effects from forest bathing, or phytoncides, which are aromatic essential oils emitted mainly by trees, of which the major ingredients are organic compounds called terpenoids (Hong et al. 2004;Li et al. 2009Li et al. , 2010. Indeed, forest bathing and exposure to phytoncides decreased the stress hormone levels in human urine (Li et al. 2009;Li and Kawada 2011). In addition, phytoncides reduced stress-induced elevation of blood pressure in stroke-prone spontaneously hypertensive rats (Kawakami et al. 2004). ...
... Previous studies have shown stress relaxing effects from forest bathing, or phytoncides, which are aromatic essential oils emitted mainly by trees, of which the major ingredients are organic compounds called terpenoids (Hong et al. 2004;Li et al. 2009Li et al. , 2010. Indeed, forest bathing and exposure to phytoncides decreased the stress hormone levels in human urine (Li et al. 2009;Li and Kawada 2011). In addition, phytoncides reduced stress-induced elevation of blood pressure in stroke-prone spontaneously hypertensive rats (Kawakami et al. 2004). ...
... Por ello hay que diseñar lo que serían hábitos saludables para el individuo: ejercicio, alimentación, reposo adecuado, contacto con los elementos naturales (17); todas las actitudes que favorezcan la capacidad de nuestro cuerpo de responder ante modificaciones que se le presenten, es decir, la capacidad de responder ante la enfermedad. ...
... The shift in stress physiology, lowered stress hormones in particular, has also been proposed to explain the improvement in immune functioning of subjects involved in various forest medicine studies. Compared to time spent in urban built environments, visits to forest settings have been shown to improve natural killer cell activity and the production of anti-cancer proteins [25]. The consistent preference for natural scenic views over urban streets is well documented, indeed the preferences for nature scenes are apparent even when they are presented for a mere 1/100 th of a second [26,27]. ...
The healing power of nature, vis medicatrix naturae, has traditionally been defined as an internal healing response designed to restore health. Almost a century ago, famed biologist Sir John Arthur Thomson provided an additional interpretation of the word nature within the context of vis medicatrix, defining it instead as the natural, non-built external environment. He maintained that the healing power of nature is also that associated with mindful contact with the animate and inanimate natural portions of the outdoor environment. A century on, excessive screen-based media consumption, so-called screen time, may be a driving force in masking awareness of the potential benefits of nature. With global environmental concerns, rapid urban expansion, and mental health disorders at crisis levels, diminished nature contact may not be without consequence to the health of the individual and the planet itself. In the context of emerging research, we will re-examine Sir J. Arthur Thomson's contention that the healing power of the nature-based environment - green space, forests and parks in particular - extends into the realm of mental health and vitality.
Evidence of the effect of contact with natural areas on people's health.
Els professionals de la conservació del patrimoni natural, per sort o per desgràcia, ens trobem contínuament amb la ne-cessitat de justificar el perquè de la nostra feina. Al llarg de la història del nostre sector hem anat explorant diferents apro-ximacions a la qüestió: des d'intentar explicar el valor patri-monial d'espècies i hàbitats per se fins a l'intent d'avaluació econòmica dels productes i serveis que els sistemes naturals ens proveeixen. I és que com més urbana es va tornant la nos-tra societat, més cal recordar allò que intuïtivament ja saben els que es dediquen a la producció primària no intensiva: l'espècie humana forma part del sistema natural i com a tal, s'hi troba bé. Des de la Fundació Catalunya-La Pedrera, es van orga-nitzar unes jornades els proppassats 22 i 23 de setembre per donar a conèixer els resultats dels primers estudis científics que busquen evidències de la hipòtesi que el contacte directe amb els sistemes naturals afavoreix la salut de les persones (Fig. 1). Aquest escrit busca ser un recull dels punts que, a criteri del tot subjectiu dels autors, poden ser més rellevants pel nostre sector. Les presentacions realitzades, els ponents que hi van participar i les gravacions de les ponències estan disponibles al web: www.fundaciocatalunya-lapedrera.com/ ca/territori-i-mediambient/salut-i-natura Per començar, voldríem destacar de la primera ponència sobre el projecte europeu PHENOTYPE a càrrec de Mark Nieuwenhuijsen del Centre de Recerca en Epidemiologia Ambiental de Barcelona (CREAL), el recull d'articles cien-tífics que evidencien la percepció intuïtiva que els espais naturals ajuden a reduir l'impacte de malalties a la població o a afavorir la recuperació dels pacients. N'hi ha molts. Desta-quem com a primera cita un article d'Ulrich (1984) publicat a Science on es recollia que els pacients d'un hospital que es recuperaven de cirurgia de vesícula en habitacions amb vis-tes a zones verdes es recuperaven abans i necessitaven menys calmants que els pacients allotjats en habitacions sense vis-tes a zones verdes; a més, tenien millor percepció del tracte rebut pel personal d'infermeria. També que la recuperació davant d'una situació estressant és més ràpida si la persona s'exposa a zones verdes (Ulrich et al., 1991); que les per-sones que caminen habitualment en zones verdes viuen més anys segons un estudi realitzat al Japó (Takano et al., 2002)
본 연구는 인체에 이로운 효과, 특히 항암 효과가 있는 것으로 알려진 삼림욕과, 그 삼림욕이 이러한 효과를 가지는 대표적인 원인인 피톤치드(phytoncide)의 항암 효과를 확인하는 것을 목적으로 한다. 마우스를 이용한 암 이식 모델을 피톤치드에 노출한 후 이식 암세포의 생장 억제와 마우스 비장에서 추출한 자연 살해 세포 (NK 세포)가 표적 세포를 죽이는 독성(cytotoxicity) 측정을 통해 피톤치드의 항암 효과를 검증했다. 피톤치드를 향으로 3주간 처리하였을 때 마우스에 이식된 암의 생장을 최대 40.96% 억제하였고, 비장의 NK 세포 활성도를 최고 약 50% 정도 증가시켰다. 이 결과는 피톤치드가 향으로 흡입되어 체내에 노출되었을 때 자연 살해 세포 활성도를 증진시키는 과정을 통해 항암 효과가 있음을 시사한다.
Civilization illnesses today impact, and will impact in the future, everyday life of people, particularly in high-income countries. Consequences are loss in life expectancy, reduction of quality of life as well as rising economic loads. The positive effects of stays and visits in natural environments on human well-being are known for a long time. Particularly, there are many indications that forest stays have health-promoting effects. This narrative review of the literature presents the current state of the research on health-promoting effects of forest exposure. Forest exposure has positive health effects on the cardiovascular system, the immune system and on mood. Especially in the context of stress reduction, forest exposure seems to have positive influences. However, little can be concluded about the extent of these positive effects, as most studies work without control environment or control groups. Moreover forest exposure is often associated with physical activity which is also known to have health benefits. Against the background of the positive health promoting trend further research should be carried out.
Les maladies de civilisation affectent aujourd’hui et affecteront encore à l’avenir la vie des gens, en particulier dans les pays à revenu élevé. Les conséquences en sont à la fois une perte de durée et de qualité de la vie et l’augmentation des charges économiques. Les effets positifs des séjours dans la nature sur le bien-être humain sont connus depuis longtemps. En outre, de nombreux indices montrent qu’en particulier les séjours en forêt ont des effets bénéfiques sur la santé. Cette revue narrative de littérature présente l’état actuel de la recherche sur les effets favorables des séjours en forêt sur la santé et propose plusieurs approfondissements. Parmi les effets bénéfiques sur la santé des séjours en forêt, des effets positifs sont observés sur les maladies cardiovasculaires, le système immunitaire et l’humeur. Plus spécifiquement, la forêt semble avoir une influence favorable sur la réduction du stress. Il est néanmoins difficile de tirer des conclusions quant à l’ampleur de ces effets bénéfiques, certaines études ne se déroulant pas dans un environne-ment contrôlé, ou ne présentant pas de groupe de contrôle. Par ailleurs, les séjours et visites en forêt sont souvent associés à une activité physique, elle-même présentant des effets bénéfiques sur la santé. Des recherches supplémentaires sont donc nécessaires pour mieux comprendre l’effet favorable de la forêt sur la santé.
We previously found that forest environments significantly increased human natural killer activity, suggesting the preventive effect of forest environments on cancer. To explore whether forest coverage affects the rate of deaths due to cancers in Japan, we investigated the relationships between the percentage of forest coverage and standardized mortality ratios due to cancers in all prefectures in Japan. Data on the percentage of forest coverage in all prefectures in Japan were collected from the database of the Forestry Agency of Japan. Data on standardized mortality ratios (SMR) due to lung, stomach, kidney, and colon cancers in males and females, breast and uterine cancers in females, and prostate cancer in males, and data of smoking status of males and females in all prefectures in Japan were collected from the database of the Ministry of Health, Labor, and Welfare of Japan. Human development index was used as a parameter of the socioeconomic status of each prefecture. The correlation and partial correlation coefficients between the percentage of forest coverage and SMR of cancers, after controlling for the effects of smoking and the socioeconomic status, were calculated. People living in areas with lower forest coverage had significantly higher SMR of cancers compared with the people living in areas with higher forest coverage. There were significant inverse correlations between the percentage of forest coverage and the SMR of lung, breast, and uterine cancers in females, and the SMR of prostate, kidney, and colon cancers in males in all prefectures in Japan, even after the effects of smoking and socioeconomic status were factored in. Taken together, these findings indicate that increased forest coverage may partially contribute to a decrease in mortality due to cancers in Japan.
Objectives: We used the POMS test to investigate the psychological effects of trips to a forest in both males and females. Methods: Three experiments were conducted. 1) Twelve healthy male subjects, aged 37-55 years, and 13 healthy female subjects, aged 25-43 years, experienced a threeday/two-night trip to forest fields. On day 1, subjects walked for two hours in the afternoon in a field; and on day 2, they walked for two hours each in the morning and afternoon, at two different fields. 2) Sixteen healthy males, aged 36-77 years, experienced day trips to an urban area and a forest park in the suburbs of Tokyo. They walked for two hours each in the morning and afternoon, in the forest park/urban area on a Sunday. 3) 53 and 98 subjects experienced a 2-hour walk in a forest field and a city park, respectively. The POMS test was conducted before, during, and after the trip/walk. Results: The three-day excursion significantly increased the score for vigor and decreased the scores for anxiety, depression and anger in males; and significantly increased the score for vigor and decreased the scores for anxiety, depression, anger, fatigue, and confusion in females. The day trip to the forest park or urban area also significantly decreased the scores for anxiety, depression, anger, and confusion; however, only the trip to the forest park significantly increased the score for vigor and decreased the scores for fatigue in male subjects. The 2-hour walk in a city park with a good density of trees or in a forest field also significantly increased the score for vigor and decreased the scores for anxiety, depression, anger, fatigue, and confusion in both male and female subjects. Conclusions: Walking significantly decreased the scores for anxiety, depression, anger, fatigue and confusion; however only walking in forest fields, not in a city area, significantly increased the score for vigor.
Humans have enjoyed forest environments for ages because of the quiet atmosphere, beautiful scenery, mild climate, special good smell, and fresh, clean air. In Japan, since 2004, a serial studies have been conducted to investigate the effect of forest bathing trips on human health. A new science called Forest Medicine was established in 2012. The Forest Medicine is a new interdisciplinary science, belonging to the categories of alternative medicine, environmental medicine and preventive medicine, which encompasses the effects of forest environments on human health. It has been reported that forests have the following beneficial effects on human health. 1 Forest bathing can increase human natural killer (NK) activity and the number of NK cells and the intracellular levels of anti-cancer proteins suggesting the preventive effect on cancers. 2 Forest bathing can reduce blood pressure, heart rate, stress hormones such as urinary adrenaline and noradrenaline and salivary cortisol. 3 Forest bathing can increase the activity of parasympathetic nerve and reduce the activity of sympathetic nerve. 4 Forest bathing also can increase the levels of serum adiponectin and dehydroepiandrosterone sulfate. 5 Forest bathing also can reduce the scores for anxiety, depression, anger, fatigue and confusion and increased the score for vigor in the POMS test showing psychological effect. 6. Forest bathing also can reduce blood glucose levels in diabetic patients. 7 These findings suggest that forest bathing may have preventive effects on life-style related disease.
Since 2004, a serial studies have been conducted to investigate the effect of forest environments on human immune function in both males and females in Japan. This review focuses on effects of forest bathing trips on human immune function. Subjects participated in a three-day/two-night trip or a day trip to a forest area, and blood and urine were sampled on days 2, 3, 7, and 30 during or after the trips. Natural killer (NK) activity and the numbers of NK, NKT and granulysin (GRN), perforin, and granzymes A/B (GrA/B)-expressing lymphocytes in blood, the levels of IL-6, IL-10, IL-12 and IL- 18, TNF-alpha in plasma and concentration of urinary adrenaline were measured. The same measurements were made before the trips on a normal working day as a control. The NK activity and the numbers of NK, NKT, GRN, perforin, and GrA/B-expressing cells on forest bathing days were significantly higher than those on the control days, whereas the concentration of urinary adrenaline on forest bathing days were significantly lower than that on the control days in both males and females. The increased NK activity lasted for more than 30 days after the trip. This suggests that if people take a forest bathing trip once a month, they may be able to maintain a higher level of NK activity. In contrast, a city trip did not increase NK activity, the numbers of NK cells, or the level of intracellular GRN, perforin, and GrA/B. These findings indicate that forest bathing trips increased NK activity, which was mediated by increases in the number of NK cells and the levels of intracellular GRN, perforin, and GrA/B. Phytoncides released from trees and the decreased production of stress hormones may partially contribute to the increased NK activity. Because NK cells can kill tumor cells by releasing anti-cancer proteins, and visiting forests increases NK activity and the amount of anti-cancer proteins; therefore, the above findings suggest that visiting forests may have a preventive effect on cancer generation and progression.
We previously reported that the forest environment enhanced human natural killer (NK) activity, the number of NK cells, and intracellular levels of anti-cancer proteins in lymphocytes, and that the increased NK activity lasted for more than 7 days after trips to forests in both male and female subjects. To explore the factors in the forest environment that activated human NK cells, we investigated the effect of essential oils from trees on human immune function both in vitro and in vivo. In the in vitro study, we investigated the effect of 8 kinds of phytoncides (wood essential oil) on NK activity and the expression of perforin, granzyme A (GrA) and granulysin (GRN) in human NK cells. We found that phytoncides significantly increased NK activity in a dose-dependent manner and significantly increased the expression of perforin, GrA and GRN. The phytoncides also partially restored NK activity and perforin, GrA and GRN levels reduced by DDVP. We found that pretreatment with phytoncides partially prevented the DDVP-induced inhibition of NK activity. These findings suggest that phytoncides can increase human NK activity. In the in vivo study, twelve healthy male subjects, aged 37-60 years, were put up in urban hotel for 3 nights. Aromatic volatile substances (phytoncides) were produced by vaporizing Chamaecyparis obtusa stem oil with a humidifier in the hotel room during the night. Blood was sampled on the last day and urine was sampled every day during the stay. Similar control measurements were made before the stay on a normal working day. The concentrations of phytoncides in hotel room air were measured. Phytoncide exposure significantly increased NK activity and the numbers of NK, perforin, GRN, and GrA/B-expressing cells, and significantly decreased the concentrations of adrenaline and noradrenaline in urine. These findings indicate that phytoncide exposure and decreased stress hormone levels partially contribute to increased NK activity.
We previously reported that the forest environment enhanced human natural killer (NK) activity, the number of NK cells, and intracellular levels of anti-cancer proteins in lymphocytes, and that the increased NK activity lasted for more than 7 days after trips to forests in both male and female subjects. To explore the factors in the forest environment that activated human NK cells, we investigated the effect of essential oils from trees on human immune function both in vitro and in vivo. In the in vitro study, we investigatedthe effect of 8 kinds of phytoncides (wood essential oil) on NK activity and the expression of perforin, granzyme A (GrA) and granulysin (GRN) in human NK cells. We found that phytoncides significantly increased NK activity in a dose-dependent manner and significantly increased the expression of perforin, GrA and GRN. The phytoncides also partially restored NK activity and perforin, GrA and GRN levels reduced by DDVP. We found that pretreatment with phytoncides partially prevented the DDVP-induced inhibition of NK activity. These findings suggest that phytoncides can increase human NK activity. In the in vivo study, twelve healthy male subjects, aged 37-60 years, were put up in urban hotel for 3 nights. Aromatic volatile substances (phytoncides) were produced by vaporizing Chamaecyparis obtusa stem oil with a humidifier in the hotel room during the night. Blood was sampled on the last day and urine was sampled every day during the stay. Similar control measurements were made before the stay on a normal working day. The concentrations of phytoncides in hotel room air were measured. Phytoncide exposure significantly increased NK activity and the numbers of NK, perforin, GRN, and GrA/B-expressing cells, and significantly decreased the concentrations of adrenaline and noradrenaline in urine. These findings indicate that phytoncide exposure and decreased stress hormone levels partially contribute to increased NK activity.
Since 2004, a serial studies have been conducted to investigate the effect of forest environments on human immune function in both males and females in Japan. This review focuses on effects of forest bathing trips on human immune function. Subjects participated in a three-day/two-night trip or a day trip to a forest area, and blood and urine were sampled on days 2, 3, 7, and 30 during or after the trips. Natural killer (NK) activity and the numbers of NK, NKT and granulysin (GRN), perforin, and granzymes A/B (GrA/B)-expressing lymphocytes in blood, the levels of IL-6, IL-10, IL-12 and IL-18, TNF-alpha in plasma and concentration of urinary adrenaline were measured. The same measurements were made before the trips on a normal working day as a control. The NK activity and the numbers of NK, NKT, GRN, perforin, and GrA/B-expressing cells on forest bathing days were significantly higher than those on the control days, whereas the concentration of urinary adrenaline on forest bathing days were significantly lower than that on the control days in both males and females. The increased NK activity lasted for more than 30 days after the trip. This suggests that if people take a forest bathing trip once a month, they may be able to maintain a higher level of NK activity. In contrast, a city trip did not increase NK activity, the numbers of NK cells, or the level of intracellular GRN, perforin, and GrA/B. These findings indicate that forest bathing trips increased NK activity, which was mediated by increases in the number of NK cells and the levels of intracellular GRN, perforin, and GrA/B. Phytoncides released from trees and the decreased production of stress hormones may partially contribute to the increased NK activity. Because NK cells can kill tumor cells by releasing anti-cancer proteins, and visiting forests increases NK activity and the amount of anti-cancer proteins; therefore, the above findings suggest that visiting forests may have a preventive effect on cancer generation and progression.
Traditional thinking considered the nervous system, endocrine system and immune system to be independent of each other. However, it is now widely accepted that they interact through the psycho-neuro-endocrino-immune network. The nervous system affects the endocrine and immune systems by releasing neurotransmitters through the hypothalamus in the hypothalamic-pituitary portal circulation. The endocrine system affects the nervous and immune systems by secreting hormones and the immune system feeds back to the nervous and endocrine systems via cytokines. This chapter will review the effects of forest environments on the human psycho-neuro-endocrino-immune network.
Forest environments affect the human immune system and sympathetic and parasympathetic nervous systems. They also alter levels of some hormones. This chapter reviews the effect of forest environments on the endocrine system. Walking in the forest setting can significantly reduce urinary levels of adrenaline and noradrenaline, stress hormones, in both males and females, as well as the concentration of cortisol in saliva. However, the effects on serum cortisol levels are inconsistent. Forest environments also have beneficial effects on adiponectin, a hormone in serum produced specifically by adipose tissue, and dehydroepiandrosterone sulfate (DHEA-S), a secretory product of the adrenal gland, the levels of which decline dramatically with age. On the other hand, forest environments did not affect serum estradiol and progesterone levels in females, or serum insulin, free triiodothyronine and thyroid-stimulating hormone levels in males.
We investigated the effects of an essential oil from Chamaecyparis obtusa (EOCO) on early life stress, using maternal separation (MS) rats and a microarray method to analyze the changes in gene expressions caused by EOCO in the hippocampus of MS rats. Rats in the MS groups were separated from their respective mothers from postnatal day (pnd) 14 to 28. Rats in the EOCO-treated groups were exposed to EOCO for 1 or 2 h by inhalation from pnd 21 to 28. The EOCO-treated MS rats showed decreased anxiety-related behaviors compared with the untreated MS rats in the elevated plus-maze (EPM) test. In the microarray analysis, we found that EOCO downregulated the expressions of cytokine genes such as Ccl2, Il6, Cxcl10, Ccl19, and Il1rl in the hippocampus of MS rats, and also confirmed that using reverse transcriptase - PCR. In particular, the expressions of Ccl2 and Il6 were predominantly decreased by EOCO in the hippocampus of MS rats. Interestingly, protein expression was also reduced by EOCO in MS rats. These results indicate that EOCO decreases MS-induced anxiety-related behaviors, and modulates cytokines, particularly Ccl2 and Il6, in the hippocampus of MS rats.
In Japan, a forest bathing trip, called "Shinrinyoku" in Japanese, is a short, leisurely visit to a forest; it is regarded as being similar to natural aromatherapy. This review focuses on the effects of forest bathing trips on human immune function. Beginning in 2005, adult Japanese individuals, both male and female, participated in a series of studies aimed at investigating the effect of forest bathing trips on human immune function. The subjects experienced a 3-day/2-night trip to forest areas, and blood and urine were sampled on days 2 (the first sampling during each trip) and 3 (the second sampling during each trip), and on days 7 and 30 after the trips. Natural killer (NK) activity, the numbers of NK, granulysin-, perforin-, and granzymes A/B-expressing lymphocytes in the blood, and the concentration of urinary adrenaline were measured. The same measurements were made before the trips on a normal working day as a control. The mean values of NK activity and the numbers of NK, granulysin-, perforin-, and granzymes A/B-expressing cells on forest bathing days were significantly higher than those on the control days, whereas the mean values of the concentration of urinary adrenaline on forest bathing days were significantly lower than that on the control days in both male and female subjects. The increased NK activity lasted for more than 30 days after the trip, suggesting that a forest bathing trip once a month would enable individuals to maintain a higher level of NK activity. In contrast, a visit to the city as a tourist did not increase NK activity, the numbers of NK cells, or the level of intracellular granulysin, perforin, and granzymes A/B. These findings indicate that forest bathing trips resulted in an increase in NK activity, which was mediated by increases in the number of NK cells and the levels of intracellular granulysin, perforin, and granzymes A/B.
This paper reviews previous research on the physiological effects of Shinrin-yoku (taking in the forest atmosphere or forest bathing), and presents new results from field experiments conducted in 24 forests across Japan. The term Shinrin-yoku was coined by the Japanese Ministry of Agriculture, Forestry, and Fisheries in 1982, and can be defined as making contact with and taking in the atmosphere of the forest. In order to clarify the physiological effects of Shinrin-yoku, we conducted field experiments in 24 forests across Japan. In each experiment, 12 subjects (280 total; ages 21.7 +/- 1.5 year) walked in and viewed a forest or city area. On the first day, six subjects were sent to a forest area, and the others to a city area. On the second day, each group was sent to the other area as a cross-check. Salivary cortisol, blood pressure, pulse rate, and heart rate variability were used as indices. These indices were measured in the morning at the accommodation facility before breakfast and also both before and after the walking (for 16 +/- 5 min) and viewing (for 14 +/- 2 min). The R-R interval was also measured during the walking and viewing periods. The results show that forest environments promote lower concentrations of cortisol, lower pulse rate, lower blood pressure, greater parasympathetic nerve activity, and lower sympathetic nerve activity than do city environments. These results will contribute to the development of a research field dedicated to forest medicine, which may be used as a strategy for preventive medicine.
The aim of this study was to evaluate the influence of the method of delivery, the level of cord blood lidocaine, and the cortisol concentration on the cord blood natural killer (NK) activity in the full-term healthy newborn. We studied healthy newborns delivered by elective cesarean section without labor under general anesthesia (n = 24), delivered by cesarean section under epidural anesthesia (n = 21), and delivered vaginally with uncomplicated labor (n = 19). The NK cell activity was significantly lower in newborns delivered by cesarean section under epidural anesthesia than it was in the general anesthesia group, while it was similar to the levels found in vaginally delivered newborns. The cortisol concentration was highest in the vaginal delivery group (589.2 ± 200 mmol/l) and lowest in the general anesthesia group (199.2 ± 81.9 mmol/l). The mean serum lidocaine concentration was 414.1 ± 370 μg/l in the epidural anesthesia group and undetectable in the other groups. In conclusion, our data suggest that the cord blood NK activity was significantly influenced by the method of delivery. This effect could be related to anesthetics given to the mother for general or epidural anesthesia or to the endocrine-metabolic variations observed after different degrees of delivery-related stress. The NK cells being a first-line defense mechanism against viral infections, the results of this study suggest an association with the occurrence of early perinatal infections, especially in preterm infants.Copyright © 1999 S.Karger AG, Basel
Objectives: To explore whether forest coverage affects the rate of deaths due to cancers in Japan, we investi-gated the relationships between the percentage of forest coverage and standardized mortality ratios due to cancers in all prefectures in Japan. Methods: Data on the percentage of forest coverage in all prefectures in Japan were collected from the database of the Forestry Agency of Japan. Data on standardized mortality ratios (SMR) due to lung, stomach, kidney, and colon cancers in males and females, breast and uterine cancers in females, and prostate cancer in males, and data of smoking status of males and females in all prefectures in Japan were collected from the database of the Ministry of Health, Labour, and Welfare of Japan. Human development index (HDI) was used as a parameter of the socioeconomic status of each prefec-ture. The correlation and partial correlation coefficients between the percentage of forest coverage and SMR of cancers, after controlling for the effects of smoking and the socioeconomic status, were calculated. Results: People living in areas with lower forest coverage had significantly higher SMR of cancers compared with the people living in areas with higher forest coverage. There were significant inverse correlations between the percentage of forest coverage and the SMR of lung, breast, and uterine cancers in females, and the SMR of prostate, kidney, and colon cancers in males in all prefectures in Japan, even after the effects of smoking and socioeconomic status were factored in. Conclusions: These findings indicate that increased forest coverage may partially contribute to a decrease in mortality due to cancers in Japan.
The effector cells mediating antibody dependent cellular cytotoxicity (ADCC) and spontaneous cellular cytotoxicity (SCC) in humans have been reported to possess similar characteristics. Multiple cell separation techniques were employed in an attempt to physically separate and distinguish the effector cells in these two types of cellular cytotoxicity. Subpopulations of mononuclear cells obtained by a variety of fractionation procedures which either enriched or depleted monocytes, lymphocytes bearing a receptor for sheep erythrocytes (SRBC), a receptor for complement (CRL) or an Fc receptor for IgG always had similar effects on both ADCC and SCC. Aggregated gamma globulin blockade of Fc receptors produced similar dose-dependent depressions of ADCC and SCC. Despite our inability to physically separate the effector cells of ADCC and SCC, administration of in vivo dexamethasone caused a relative increase in ADCC but a profound decrease in SCC. Furthermore, in vitro dexamethasone in pharmacologic and suprapharmacologic concentrations caused no change in ADCC but significantly decreased SCC. This study demonstrates that although the effector cells cannot be physically separated, ADCC and SCC are differentially sensitive to corticosteroids and are hence functionally distinct either on the basis of different subsets of effector cells with similar surface markers or different mechanisms of cytotoxicity by the same effector cell.
The aim of the study was to test the cytotoxic activity of peripheral blood natural killer (NK) cells in relation to serum levels of sex hormones in patients with mastopathy. The study included 37 patients classified into mastalgia, fibrosis, fibrocystic disease, and fibroadenoma groups and 19 healthy age-matched volunteer women. Estradiol, progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin were evaluated in sera by specific radioimmunoassays. NK cell activity was evaluated by means of 51Cr-release assay. In all patient groups, progesterone levels were significantly decreased. There was also an increased frequency of patients with low levels of estradiol (< 50 pg/ml). On the other hand, LH levels in fibrocystic disease and fibroadenoma groups were significantly increased. NK cell activity was in the normal range in all patient groups. In individual women, NK cell cytotoxicity did not correlate with the levels of the studied hormones. However, in patients with low (< 50 pg/ml) and high (> 200 pg/ml) estradiol levels an increase and a decrease of NK cell activity was observed, respectively. This suggests that in patients with mastopathy, estradiol may directly or indirectly affect NK cell cytotoxicity. High levels of estradiol and low NK cell activity might constitute an increased risk for neoplasia.
Natural killer (NK) cells are CD3- CD56+ and/or CD16+ cytotoxic lymphocytes that mediate first-line defense against various types of target cells without prior immunization. To assess the effect of the menstrual cycle and gender on NK activity we evaluated 30 healthy women (mean age 28.1 years, range 21-39) in follicular and luteal phases, 29 postmenopausal women (mean age 58.8 years, range 42-72) and 48 healthy men (mean age 31.6 years, range 21-40). In a flow cytometric test of NK activity, peripheral blood mononuclear effector cells were mixed with K562 targets cells labeled with DiO (3,3'-dioctadecyloxacarbocyanine perchlorate) at effector:target cell ratios of 40, 20, 10 and 5:1. Dead cells were stained with propidium iodide and results were expressed as lytic units per 10(7) cells. In addition, progesterone levels were determined in the luteal phase of the menstrual cycle of healthy women by a chemiluminescence assay. Our results showed that (1) NK cytotoxicity was higher in the follicular than in the luteal phase of the menstrual cycle (P < 0.0001); (2) postmenopausal women and men showed NK activity similar to women in the follicular phase but higher than women in the luteal phase of the menstrual cycle (P < 0.05); and (3) there was no correlation between NK activity and levels of progesterone. The data suggest that progesterone does not influence NK activity directly and that other factors may explain the reduction of NK activity in the luteal phase of the menstrual cycle.
We have previously found that diisopropyl methylphosphonate, an organophosphorus by-product generated during sarin synthesis in the Tokyo sarin disaster, significantly inhibited natural killer (NK) and cytotoxic T lymphocyte (CTL) activities. In the present study, to investigate whether organophosphorus pesticides (OPs) also affect NK and CTL activities, we firstly examined the effect of five OPs on human NK activity, and then the effect of Dimethyl 2,2-dichlorovinyl phosphate (DDVP), an OP on murine splenic NK, CTL and lymphokine-activated killer (LAK), and human LAK activities in vitro. To explore the underlying mechanism of decreased NK activity, we also investigated the effect of 4-(2-aminoethyl) benzenesulfonyl fluoride-HCl (p-ABSF), an inhibitor of serine proteases on NK, LAK and CTL activities, and the effect of DDVP on the activity of granzymes (serine proteases). We found that OPs significantly decreased human NK activity in a dose-dependent manner, but the degree of decrease in NK activity differed among the OPs investigated, and that DDVP significantly decreased NK, LAK and CTL activities in a dose-dependent manner, but the degree of decrease in these activities differed. p-ABSF showed a similar inhibitory pattern to DDVP, and had an additive inhibitory effect with DDVP on NK, LAK and CTL activities. We also found that DDVP significantly inhibited granzyme activity in a dose-dependent manner. These findings indicate that OPs significantly decrease NK, LAK and CTL activities in vitro via granzyme inhibition.
Natural killer (NK), lymphokine-activated killer (LAK) and cytotoxic T lymphocyte (CTL) cells induce target cell death by two main mechanisms, the perforin/granzyme pathway and the Fas-ligand (FasL)/Fas pathway. We have previously found that organophosphorus pesticides significantly inhibit human and murine NK, LAK and CTL activities and that this inhibition is partially mediated by the inhibition of granzymes. We asked here whether organophosphorus pesticides also affect the FasL/Fas pathway by using perforin-knockout (PKO) mice. Thus, we examined the effect that dimethyl 2,2-dichlorovinyl phosphate (DDVP), an organophosphorus pesticide has on NK, CTL and LAK activities of PKO mice in vitro using the Fas antigen-positive YAC-1 cell as a target in the present study. We found that DDVP significantly decreased NK, CTL and LAK activities in a dose-dependent manner, and that the CTL and LAK activities of PKO mice were significantly blocked by anti-FasL antibody, suggesting that DDVP and anti-FasL antibody have the same/similar mechanism of inhibiting LAK and CTL activities. We further found that DDVP decreases the expression of Fas antigen on YAC-1 cells, and the expression of FasL on LAK cells in a dose-dependent manner, respectively. Taken together, these findings indicate that the DDVP-induced inhibition of NK, LAK and CTL activities in PKO mice is mediated by the impairment of the FasL/Fas pathway.
Natural killer (NK), lymphokine-activated killer (LAK) and cytotoxic T lymphocyte (CTL) cells kill target cells by the directed release of cytolytic granules that contain perforin, granzymes and granulysin. We previously have found that dimethyl 2,2-dichlorovinyl phosphate (DDVP), an organophosphorus pesticide significantly inhibited NK, LAK and CTL activities via the inhibition of granzyme activity. To further explore the mechanism of organophosphorus pesticide-induced inhibition of cell-mediated cytolysis, we asked here whether organophosphorus pesticides affect the expression of perforin, granzyme and granulysin in NK cells. We used NK-92CI cell, an interleukin-2 (IL-2) independent human NK cell line. We confirmed that NK-92CI cells express CD56 surface marker, perforin, granzyme A and granulysin by flow cytometry and immunofluorescence microscope, and that it is highly cytotoxic to K562 cells in chromium release assay. We found that DDVP significantly decreases the expression of perforin, granzyme A and granulysin in NK-92CI cells in a dose-dependent manner. Immunocytochemical results showed that DDVP significantly decreases perforin, granzyme A and granulysin positive granules in NK-92CI cell, which may be due to the degranulation. We also found that DDVP have a modest, but a significant inhibitory effect on the transcription of mRNA of perforin, granzyme A and granulysin.
To explore the mechanism of stress-induced inhibition of natural killer (NK) activity, female C57BL/6 mice were stimulated by electric foot shock and psychological stress for 7 days consecutively. The shocked mice received scrambled, uncontrollable, inescapable 0.6 mA electric shocks in a communication box 120 times during 60 min. The mice in the psychological stress group were put into the communication box without electric foot shock. The plasma corticosterone level in both stressed groups was significantly higher than that in controls on days 1, 3, 5 and 7 and showed the highest level on day 3 in the foot shock stress. According to these results, therefore, we investigated the effect of stress on immunological function on day 3, and measured body weight, weight of the spleen, number of splenocytes, splenic NK, lymphokine-activated killer (LAK) and cytotoxic T lymphocyte (CTL) activities, NK receptors, and mRNA transcripts for granzymes A and B and perforin in splenocytes. The NK, LAK and CTL activities, and NK receptors in mice with both types of stress were significantly decreased compared to those of the control mice, but the decreases were greater in the foot-shocked mice than in the psychological-stress mice. The mRNA transcripts for granzyme A and perforin were significantly decreased only in the foot-shocked mice. On the other hand, the foot-shock stress increased granzyme B. The above findings suggest that stress induced inhibition of NK, LAK and CTL activities partially via affecting NK receptors, granzymes and perforin.
The two objectives are to test the hypothesis that women in a profession with low decision latitude will have greater catecholamine excretion and higher blood pressure than women in a profession with greater decision latitude, and to assess the influence of ethnicity on the occupational comparison.
Premenopausal women who were either full-time teachers in public schools (teachers; N = 92) or nurses or nurse's aides (nurses; N = 55) in East Hawaii who were not currently taking antihypertensive medication had ambulatory blood pressure (BP) and urinary catecholamine excretion measured over an approximate 4-hour period at work and home and over an approximate 8-hour period overnight. The women also filled out the Job Content Questionnaire (JCQ).
The nurses had significantly lower scores on the "decision latitude" subscale of the JCQ. After controlling for the effects of ethnicity, age, body mass index, JCQ subscale scores, smoking habits, and menopausal status in regression analyses, the nurses also had significantly higher mean systolic and diastolic BP both in work and home settings and higher mean rates of both norepinephrine and epinephrine excretion in all daily settings (p < .05). There were no significant ethnic differences in scores on the JCQ subscales, but Asian-Americans had significantly higher systolic BP in all daily settings and higher diastolic BP overnight (p < .05) than Euro-Americans.
These results suggest that among professional women, physiological stress responses are significantly greater when occupation-related decision latitude is low (nurses) than when it is high (teachers). The physiological response to stress is carried over into the home and overnight settings when occupation-related decision latitude is low (nurses). Individual scores on the JCQ were not significantly related to physiological measures in this study, however. Inclusion of contrasting occupations may be necessary to properly evaluate the relationships between individually reported job strain and heightened physiological stress responses in studies of working women.
To explore the effect of forest bathing on the human immune system, we investigated the effect of phytoncides (wood essential oils) on natural killer (NK) activity and the expression of perforin, granzyme A and granulysin in human NK cells. We used NK-92MI cell, an interleukin-2 independent human NK cell line derived from the NK-92 cell, in the present study. NK-92MI cells express the CD56 surface marker, perforin, granzyme A, and granulysin by flow cytometry and are highly cytotoxic to K562 cells in chromium release assay. Phytoncides significantly increase cytolytic activity of NK-92MI cells in a dose-dependent manner and significantly increase the expression of perforin, granzyme A, and granulysin in the NK-92MI cells. Phytoncides also partially, but significantly, restore the decreased human NK activity and the decreased perforin, granzyme A, and granulysin expression in NK-92MI cells induced by dimethyl 2,2-dichlorovinyl phosphate (DDVP), an organophosphorus pesticide. Pretreatment with phytoncides partially prevents DDVP-induced inhibition of NK activity. Taken together, these data indicate that phytoncides significantly enhance human NK activity and this effect is at least partially mediated by induction of intracellular perforin, granzyme A, and granulysin.
It is well documented that natural killer (NK) cells provide host defense against tumors and viruses. We previously showed that lifestyle affects human NK and LAK activities. In order to explore the underlying mechanism, we investigated the effect of lifestyle on intracellular perforin, granulysin, and granzymes A/B in peripheral blood lymphocytes (PBL).
114 healthy male subjects, aged 20-59 years, from a large company in Osaka, Japan were selected with informed consent. The subjects were divided into groups reporting good, moderate, and poor lifestyles according to their responses on a questionnaire regarding eight health practices (cigarette smoking, alcohol consumption, sleeping hours, working hours, physical exercise, eating breakfast, balanced nutrition, and mental stress). Peripheral blood was taken, and numbers of NK, T, perforin, granulysin, and granzymes A/B-expressing cells in PBL were measured by flow cytometry.
Subjects with good or moderate lifestyle showed significantly higher numbers of NK, and perforin, granulysin, and granzymes A/B-expressing cells and a significantly lower number of T cells in PBL than subjects with poor lifestyle. Among the eight health practices, cigarette smoking, physical exercise, eating breakfast, and balanced nutrition significantly affect the numbers of NK, T cells, perforin, granulysin, and/or granzymes A/B-expressing cells, and alcohol consumption significantly affects the number of granzyme A-expressing cells. On the other hand, mental stress, sleeping, and working hours had no effect on those parameters.
Taken together, these findings indicate that poor lifestyle significantly decreases the numbers of NK, perforin, granulysin, and granzymes A/B-expressing cells in PBL.
Natural killer (NK), lymphokine-activated killer (LAK), and cytotoxic T lymphocyte (CTL) cells kill target cells by the directed release of cytolytic granules that contain perforin, granzymes, and granulysin. We have found previously that dimethyl 2,2-dichlorovinyl phosphate (DDVP, dichlorvos), an organophosphorus pesticide, significantly decreased the expression of perforin, granzyme A (GrA), and granulysin and inhibited NK, LAK, and CTL activities. To further explore the mechanism of organophosphorus pesticide-induced inhibition of cell-mediated cytolysis, we examined whether organophosphorus pesticides affect the expression of GrB and Gr3/K in NK cells. We used an interleukin-2 (IL-2) independent human NK cell line, NK-92CI. We confirmed that NK-92CI cells express intracellular GrB and Gr3/K by flow cytometry, that NK-92CI cells are highly cytotoxic to K562 cells with a chromium release assay, and that DDVP significantly inhibited cytolytic activity of NK-92CI cells in a dose- and time-dependent manner. We found that DDVP significantly decreased the expression of GrB and Gr3/K in NK-92CI cells in a dose- and time-dependent manner by flow cytometry. Immunocytochemical results showed that DDVP significantly decreases the level of GrB positive granules in NK-92CI cells, which may be due to degranulation. Taken together, DDVP significantly inhibits NK activity and reduces the intracellular GrB and Gr3/K levels in NK cells.