Article

1,3-β-Glucan affects the balance of Th1/Th2 cytokines by promoting secretion of anti-inflammatory cytokines in vitro

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Abstract

1,3‑β‑glucan is considered a fungal biomarker and exposure to this agent induces lung inflammation. Previous studies have shown that 1,3‑β‑glucan affects Th1 and Th2 immune responses. Interleukin (IL)‑10 and transforming growth factor (TGF)‑β, as typical anti‑inflammatory cytokines, suppress the Th1 immune response. To investigate the effects of 1,3‑β‑glucan on the secretion of cytokines in co‑cultured mouse macrophages and lymphocytes in vitro, mice were exposed to 1,3‑β‑glucan or phosphate‑buffered saline (PBS) by intratracheal instillation. Following extraction and co‑culture of macrophages and lymphocytes, which were treated with or without 1,3‑β‑glucan in vitro, enzyme‑linked immunosorbent assay (ELISA) was used to detect the levels of cytokines and real‑time reverse transcription (RT)‑polymerase chain reaction (PCR) was used to investigate the mRNA expression of forkhead box p3 (Foxp3) in the cells. We showed that 1,3‑β‑glucan exposure in vitro decreased the secretion of Th1 cytokines and increased the secretion of Th2 cytokines in the culture media. Furthermore, 1,3‑β‑glucan exposure in vitro increased the secretion of IL‑10 and TGF‑β in the culture media. According to these results, 1,3‑β‑glucan exposure in vitro is suggested to promote the secretion of anti‑inflammatory cytokines, which may lead to a decrease in the levels of Th1 cytokines and an increase in the levels of Th2 cytokines. 1,3‑β‑Glucan is suggested to induce regulatory lymphocytes, which partly contributes to an increased secretion of anti‑inflammatory cytokines in co‑cultured mouse macrophages and lymphocytes in vitro.

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... Th2 immune response" Th1 immune response; [25] b-glucans present both pro-and anti-inflammatory activities. For example, in human monocytes and macrophages, b-glucan extracted from mushroom had a distinct stimulating effect on the release of pro-inflammatory cytokines such as IL-8, IL-6, IL-1b and TNF-a [21,22]. ...
... In addition to cytokine responses, b-glucans also showed modulatory activities on the shift of T-cell response bias and the types of immunoglobulin production. For example, an in vitro experiment showed b-1,3-glucan from Saccharomyces cerevisiae improved Th2 immune response and inhibited Th1 by promoting the release of anti-inflammatory cytokines such as IL-10 and TGF-b [25], whereas the other in vivo experiment indicated a mushroom b-1,3-glucan decreased Th2 immune response induced by OVA and strengthen Th1 type immune response [26]. Nowadays, b-glucans are widely used in aquaculture and food industry partly because of their immunostimulatory activities [28][29][30]. ...
Article
β-glucans, a group of polysaccharides exist in many organism species such as mushrooms, yeasts, oats, barley, seaweed, but not mammalians, have a variety of biological activities and applications in drugs and other healthcare products. In recent years, β-glucans have been studied as adjuvants in anti-infection vaccines as well as immunomodulators in anti-cancer immunotherapy. β-glucans can regulate immune responses when administered alone and can connect innate and adaptive immunity to improve immunogenicity of vaccines. When β-glucans act as immunostimulants or adjuvants, a set of receptors have been revealed to recognize β-glucans, including dectin-1, complement receptor 3 (CR3), CD5, lactosylceramide, and so on. Therefore, this review is mainly focused on the application of β-glucans as immune adjuvants, the receptors of β-glucans, as well as their structure and activity relationship which will benefit future research of β-glucans.
... 9,15 Moreover, b-glucans have recently been reported to enhance Ag-specific T cell and B cell responses. [16][17][18] In our previous studies, it has been confirmed that WGPs accelerate the differentiation of MDSCs as well as inhibiting the suppressive function of MDSCs via Dectin-1/Syk pathway. 19 However, the molecular mechanism of regulation on MDSCs by WGP is still unknown. ...
... 30 Furthermore, it has been recently reported b-glucans enhance Ag-specific T cells and B cells responses by promoting the maturation and antigen presentation of DCs. 12,[16][17][18]31 Thus, b-glucans play a key role in the innate and adaptive immune responses. We have indicated that WGP can regulate the differentiation and immunosuppression of MDSCs as this NF-kB dependent regulation is through Dectin-1/Syk pathway. ...
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... [12,13] Some in vitro studies have also supported the beneficial effects of β-glucan on the immune system. [14,15] Studies on humans have shown that the administration of soluble fiber or intravenous β-glucan in trauma patients and in patients with severely acute pancreatitis reduced the infection, length of ICU stay, and septic morbidity. [16][17][18] Unfortunately, most studies have been done in vitro or on animals. ...
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... Glucans are well known to stimulate production and secretion of various cytokines, with a wide range from IL-1, IL-2, and IL-6 to TNFα, and IFNγ [26,27]. In fact, there is only one known glucan without any significant stimulation of cytokine production [28]. ...
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Biological and most of all immunological effects of natural immunomodulator glucan are already well established. However, since hundreds of individual glucans, isolated from various sources, used at different concentrations and having different physicochemical characteristics are being used, the current scientific knowledge is not complete. In addition, direct comparisons of individual glucans are quite rare. In the present paper, we tested fifteen varieties of glucans differing in source and solubility. Whereas no direct connection between source and immunological effects was found, we can conclude that the best glucans have pleiotropic effects stimulating all facets of immunological reactions, whereas other glucans have low effects or none at all.
... from lymph nodes during epicutaneous sensitization [44]. Conversely, β-glucan treatment can increase T H 2-cell cytokine secretion from cocultured macrophages and lymphocytes [45] and stimulate production of both proallergic (IL-33, CCL17, CCL22) and inflammatory (IL-1β and CXCL1) mediators during lung exposure to Aspergillus fumigatus, in a dectin-1-dependent manner [46]. Furthermore, in addition to TSLP we have observed that β-glucanstimulated mDCs generate large quantities of CCL22 (data not shown) emphasizing that mDCs can secrete pro-T H 2-cell factors. ...
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... On one hand, we do not need long-lasting systemic effects on cytokine production; on the other hand, immunomodulators only rarely skip this part of the defense reactions. Thus, glucans usually stimulate production of several cytokines such as IL-2, IL-10, TGFβ and IFNγ [21], with the only exception being Betafectin [22]. ...
... [12,13] Some in vitro studies have also supported the beneficial effects of β-glucan on the immune system. [14,15] Studies on humans have shown that the administration of soluble fiber or intravenous β-glucan in trauma patients and in patients with severely acute pancreatitis reduced the infection, length of ICU stay, and septic morbidity. [16][17][18] Unfortunately, most studies have been done in vitro or on animals. ...
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BACKGROUND: Trauma is associated with a profound immunological dysfunction. This predisposes patients to infections and adverse outcomes. β-glucan has been implicated in the initiation of anti-microbial immune response. The present study aimed to evaluate the effects of an enteral diet containing β-glucan on serum levels of IL-12 and highly-sensitive C-reactive protein (hs-CRP), occurrence of infection, and clinical outcomes in critically ill multiple-trauma patients. METHODS: Forty multiple-trauma patients requiring enteral nutrition for at least 10 days were randomly assigned to the intervention group (n=20) or the placebo group (n=20). The intervention group received a high-protein enteral diet providing 3 g β-glucan, and the control group received a similar diet, except for 3 g of maltodextrin as a placebo. Serum levels of IL-12 and hs-CRP were measured on days 0, 10, and 21. RESULTS: The β-glucan group showed significantly higher serum levels of IL-12 on day 21 compared to the control group. Infection frequency and duration of mechanical ventilation were significantly lower in the β-glucan group. A significant difference was found in the Sequential Organ Failure Assessment (SOFA) score in favor of the β-glucan group. No difference was found in the serum levels of hs-CRP, length of ICU stay, occurrence of infection, and mortality rates between the two groups. CONCLUSION: β-glucan may increase serum levels of IL-12, shorten the duration of mechanical ventilation, and reduce organ failure in critically ill multiple-trauma patients.
... Immunostimulators in general and glucans in particular stimulate secretion of various cytokines such as IFN-γ, IL-1, IL-2, and TNF-α (29,30,31). In our study, we measured the production of IL-2 by spleen cells. ...
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Background/aim: β-Glucans are well-established immunomodulators with strong effects across all immune reactions. Due to the extensive amount of studies, glucans are steadily progressing from a non-specific immunomodulator to a licensed drug. However, direct comparisons of higher numbers of different glucans are rare. Materials and methods: In this study, we used 16 different glucans isolated from yeasts, mushroom, algae, and oat and compared their effects on phagocytosis, IL-2 production, antibody secretion, and inhibition of three experimental cancer models. Results: Our results showed significant differences among tested glucans, showing that despite the fact that glucans in general have strong stimulating effects on most aspects of the immune system, it is necessary to choose the right glucan. Conclusion: Based on our studies, we can conclude that highly purified and active glucans have significant pleiotropic effects.
... Supplementing probiotics and MOS to calves increases performance and health including increased body weight (BW), average daily gain (ADG), and decreased fecal scores (Heinrichs et al., 2003;Ghosh and Mehla 2012). Supplementing BG previously has increased pro-inflammatory cytokine production, increased leukocyte function, and moderated the impacts of inflammation during sepsis in multiple species (Novak and Vetvicka 2009;Eicher et al., 2010;Chen, 2013). Supplementation of these compounds has shown equivocal results, and each supplement appears to have unique mechanisms of action. ...
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... After the A/ H5N1 influenza virus Vetvicka et al. [12] concluded that there are no significant differences in IL-1 β levels on glucan treated mice compared to PBS but the INF-γ increased considerably [12]. Of course, it is important to note that even the cytokine response on IL-1 β production and Th1/Th2 balance varies greatly on β -glucan size, origin, conformation and molecular mass [31][32][33], thus the particle size is essential in cytokine production and small particles led to a reduction in inflammatory gene transcription compared to large particles [31]. ...
... Inconsistent results have also been demonstrated in other animals. For example, cytokines involved in the type-2 pathway of immune responses were downregulated by βglucan in humans (72) but upregulated in mice (73). Therefore, additional investigation is needed to understand fully the effects of β-glucan on immune responses of broilers. ...
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In recent years, prebiotics have been considered as potential alternatives to antibiotics. Mechanisms by which prebiotics modulate the ecosystem of the gut include alternation of the intestinal microbiota, improvement of the epithelium, and stimulation of the immune system. It is suggested that the administration of prebiotics not only influences these aspects but also regulates the interaction between the host and the intestinal microbiota comprehensively. In this review, we will discuss how each prebiotic ameliorates the ecosystem by direct or indirect mechanisms. Emphasis will be placed on the effects of prebiotics, including mannan oligosaccharides, β-glucans, and fructans, on the interaction between the intestinal microbiota, gut integrity, and the immunity of broilers. We will highlight how the prebiotics modulate microbial community and regulate production of cytokines and antibodies, improving gut development and the overall broiler health. Understanding the cross talk between prebiotics and the intestinal ecosystem may provide us with novel insights and strategies for preventing pathogen invasion and improving health and productivity of broilers. However, further studies need to be conducted to identify the appropriate dosages and better resources of prebiotics for refinement of administration, as well as to elucidate the unknown mechanisms of action.
... Biologically active polysaccharides (e.g., β-glucans) represent a highly studied group of natural immunomodulators with pluripotent biological activities. Certain molecules are able to attenuate inflammatory cytokine release and prevent lung injury in animal models (Bedirli et al., 2007;Cao et al., 2018) and restore the cytokine imbalance by promoting the secretion of anti-inflammatory compounds (Chen et al., 2013). Another mode of action could be the support of NK cell functions and modulatory effect on T cells (Bobovak et al., 2010;Bergendiova et al., 2011;Jesenak et al., 2013). ...
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Severe acute respiratory syndrome caused by a novel 2019 coronavirus (SARS-CoV2) represents one of the most studied infectious diseases of today. The number of scientific reports and publications increases exponentially day by day. While the majority of infected subjects are asymptomatic or show mild symptoms, there is an important proportion of patients who requires hospitalization and, sometimes, intensive care. Immune response to novel coronavirus is complex, involves both innate and adaptive immunity, and is biphasic. Significant differences were observed when comparing severe and non-severe patients. Analysis of the reported results from clinical trials clearly show an involvement of specific cellular immunity (predominantly leucopenia, decreased counts of CD3+, CD4+, and CD8+ T lymphocytes, changes of T cell compartment) and the so-called cytokine storm, which is associated with worsening of symptoms and the promotion of lung damage. An interesting finding regarding eosinopenia that can have both diagnostic and prognostic value is reported by some authors. Examination of selected immune parameters could help to identify severe patients with the risk of unfavorable course of the disease, predict the prognosis and recognize improvement in the clinical status. Moreover, detailed analysis of the immune changes could help to select novel prospective therapeutic strategies.
... Binding of glucans to these receptors triggers a cascade of events resulting in the expression of pro-inflammatory cytokines, predominately TNF-α as well as cytokines IL-1, IL-2 and IL-6 (Williams et al., 2000;Majtán et al., 2005;Vetvička et al., 1996). Recently, Chen et al. (2013) reported that β-(1-3)-glucan from fungi affects the balance of Th1/Th2 cytokines by promoting secretion of anti-inflammatory cytokines in vitro and Municio et al. (2013) stated that response of human macrophages to β-glucans depends on the inflammatory milieu. ...
... In addition to direct effects on activities of immunocytes, it is assumed that the immunomodulators bind to the specific receptors with subsequent signaling resulting in cell activation and secretion of cytokines and other biologically active molecules. Immunostimulators in general and glucans in particular stimulate secretion of various cytokines [36]. Evaluating the effects on IL-2 production, our study confirmed the strong effects of isolated glucan [37]. ...
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Background: Yeast was the first microorganism used as a source of protein and it still is the main source of unicellular protein in human nutrition. Numerous yeast products and yeast derivatives are produced and used in animal feed, pet food, and human food around the world. Although the whole yeast cell and the yeast cell wall have β-1,3-1,6-glucan in their chemical composition, their immunological effects in vivo can be quite different of those of the yeast purified β-1,3-1,6-glucan. Methods: In order to study these different in vivo effects, we used a traditional package for evaluation of commercial glucans to compare the whole yeast cell, the yeast autolysate, the yeast cell wall, and the yeast purified β-1,3-1,6-glucan produced from the same original yeast raw material. We evaluated the effects of these compounds on phagocytosis, IL-2 secretion, and antibody production. Results: We found that although the whole yeast cell and the yeast cell wall have β-1,3-1,6-glucan in their chemical composition, their immunological effects in vivo can be quite different of those of the yeast purified β-1,3-1,6-glucan.All activities, ie., phagocytosis, IL-2 production and antibody production were the highest in the group supplemented with purified glucan. Conclusions: Our results suggest that the yeast derivatives have more limited immunological effects, maybe as a result of local intestinal immune reactions. The purified glucan showed stronger immunological activities.
... Glucans are well known to stimulate production and secretion of various cytokines, with a wide range from IL-1, IL-2, and IL-6 to TNFα, and IFNγ [26,27]. In fact, there is only one known glucan without any significant stimulation of cytokine production [28]. ...
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Chapter
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β-Glucans are structural cell wall polymers of many fungi which possess immunomodulatory activities. Although the therapeutic benefits associated with these compounds, particularly as anti-infective and antitumorigenic agents, have led to a large body of published research over the last five decades, it is still unclear how these carbohydrates mediate their effects. Recent studies, however, are starting to shed some light on the cellular receptors and molecular mechanisms involved, which also have direct relevance on the innate immune response to fungal pathogens.
Article
Tumor necrosis factor-alpha (TNFα) is a potent cytokine believed to participate in the development of endotoxin-induced shock and the adult respiratory distress syndrome [1,2]. Treatment of animals with β-glucan prior to bacterial challenge reduces TNFα release and prevents death [3]. We therefore hypothesized that β-glucan might regulate TNFα secretion from macrophages in response to lipopolysaccharide (LPS). Rat alveolar macrophages were cultured in the presence of β-glucan alone and the TNFα secretion quantified using an L929 cytotoxicity assay. Concentrations of β-glucan less than 500 μg/ml were found to stimulate TNFα release from macrophages. However, concentrations of β-glucan greater than 500 μg/ml resulted in suppression of the TNFα activity released. This reduction in TNFα release was not mediated by a toxic effect of β-glucan, as large concentrations of β-glucan had no effect on macrophage viability. We further observed that the incubation of macrophages with large concentrations of β-glucan (500 μg/ml) also inhibited the secretion of TNFα induced by bacterial LPS. Furthermore, interferon-γ (IFNγ), a potent activator of TNFα expression, failed to overcome the inhibition of TNFα caused by β-glucan. These data suggest an immunomodulatory role for β-glucan which may explain both the TNFα-stimulating and -inhibiting effects of fungal β-glucans during infection.
Article
The study was conducted to investigate the effects of dietary β-1,3–1,6-glucan supplementation on the reproductive performance and immunity of New Zealand White breeding does and their pups. Thirty pregnant multiparous New Zealand White does were randomly assigned to three dietary treatments; 0 (control), 0.064% β-1,3–1,6-glucan or 0.128% β-1,3–1,6-glucan dietary supplementation from day 14 of gestation to day 28 of lactation. The 0.128% dietary β-1,3–1,6-glucan supplementation caused reduced (P
Article
We investigated the effect of a fungal component, soluble �- glucan, on secretory functions of murme alveolar macrophages (AMs) in vitro. Stimulation by �-glucan (500 jigJmL) or interferon-y (IFN-'y; 100 U/mL) alone had a slight effect on AM functions, but when AMs were incubated together with �-glucan and IFN-y, the production and secre- tion of some immune mediators, such as nitric oxide, interleukin- 1 (IL- 1 ), IL-6, and tumor necrosis fac- tor-a (TNF-a), were markedly augmented. This combined effect of �-glucan and IFN-y was based on a priming effect of IFN-y, because prestimulation with IFN-y followed by (�-glucan induced high nitric oxide production of AMs, but reversal of the se- quence of treatments had only a slight effect. We also found that premcubation of AMs with IFN-? en- hanced the binding of fluorescein-labeled �-glucan on the AM surface, and this increased binding was abrogated to the control level by the addition of three species of soluble unlabeled (1 -+3)-�3-D-glucans but not by soluble a-glucan. These data imply that the priming effect of IFN-y on the AM response to �-glucan was dependent, at least in part, on the enhancement off�-glucan specific binding sites on the AM surface. It was suggested that IFN-'y is one of the principal factors controlling the pulmonary immune system against both severe fungal infection and in- flammation via AM activation at the alveoli. J. Leukoc. Biol. 60: 118-124; 1996.
Article
In this study, we compared the effects of zymosan and LPS on human monocyte-derived dendritic cells. The specific effects of zymosan on the expression of several key cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukins (IL-1α, IL-1β and IL-12 p70) were quite distinct from the effects of LPS. Unlike activation with LPS, DCs activated by zymosan expressed little or no IL-12 p70 due to lack of expression of the p35 subunit. However, treatment with zymosan resulted in a substantial increase in Th1 and Th17 cell-polarizing capacity of DCs. Furthermore, the GM-CSF secreted by zymosan-activated DCs enhanced IL-23 production, resulting in activation of a Th17 response. GM-CSF and IL-27, rather than IL-12 p70, were both major direct contributors to the activation of a Th1 response. This signaling mechanism is distinct and yet complementary to LPS-mediated T-cell activation. We suggest that this novel zymosan-induced GM-CSF-mediated signaling network may play a key role in regulating specific immune cell type activities.
Article
1,3-β-Glucan was a major cell wall component of fungus. The existing studies showed that 1,3-β-glucan exposure could induce lung inflammation that involved both Th1 and Th2 cytokines. Regulatory T cells (Treg cells) played a critical role in regulating immune homeostasis by adjusting the Th1/Th2 balance. The role of Treg cells and regulatory mechanism in 1,3-β-glucan-induced lung inflammation is still unclear. In our study, mice were exposed to 1,3-β-glucan by intratracheal instillation. To investigate the role of Treg cells in response to 1,3-β-glucan, we generated Treg-depleted mice by intraperitoneal administration of anti-CD25 mAb. The Treg-depleted mice showed more inflammatory cells and severer pathological inflammatory change in lung tissue. Depletion of Treg cells led to increased Th1 cytokines and decreased Th2 cytokines. Treg-depleted mice showed a decreased expression of anti-inflammation cytokine and lower-level expression of CTLA-4. In all, our study indicated that Treg cells participated in regulating the 1,3-β-glucan-induced lung inflammation. Depletion of Treg cells aggravated the 1,3-β-glucan-induced lung inflammation, regulated the Th1/Th2 balance by enhancing Th1 response. Treg cells exerted their modulation function depending on both direct and indirect mechanism during the 1,3-β-glucan-induced lung inflammation.
Article
Beta-1-3 Glucan is a polysaccharide extracted from Saccharomyces cerevisiae with a possible immunomodulating action that may have a favourable action on asthma symptoms and other allergic diseases. An experimental study carried out using a murine respiratory model detected a decrease in pulmonary tissue eosinophilia, as well as an increase in Interleukin-10 (IL-10) after glucan use. This open, exploratory study with blind outcome evaluation included asthmatic children between 6 and 12 years of age with mild to moderate persistent asthma and inadequate disease control (rescue medication needed more than twice a week) in spite of inhaled budesonide 400 microg/day. After a four week run-in period, subcutaneous Beta-1-3-glucan injections were given weekly for the first four weeks and then every two weeks for the last four weeks. IL-10 levels, measured by the immunoenzymatic method (ELISA), were compared before and after glucan administration. Twenty patients (14 male and 6 female) were included. Mean IL-10 levels were 6.4 pg/ml and 11.3 pg/ml before and after glucan, respectively (p = 0.02). There was also a reduction of asthmatic symptoms score at the end of study. This is the first study which shows that subcutaneous particulate Beta-1-3-glucan increases serum IL-10 levels in asthmatics. The possibility of glucan being able to modulate allergic sensitisation and having a beneficial action in restoring Th2 function should be assessed by means of properly planned controlled clinical trials, as it may represent a new therapeutic strategy.
Article
Lentinan, a (1-3)-beta glucan from Lentinus edodes, is an effective immunostimulatory drug. We tested the effects of lentinan during blood-stage infection by Plasmodium yoelii 17XL (P.y17XL). Pre-treatment of mice with lentinan significantly decreased the parasitemia and increased their survival after infection. Enhanced IL-12, IFN-gamma and NO production induced by lentinan in spleen cells of infected mice revealed that the Th1 immune response was stimulated against malaria infection. In vitro and in vivo, lentinan can result in enhanced expression of MHC II, CD80/CD86, and Toll-like receptors (TLR2/TLR4), and increased production of IL-12 in spleen dendritic cells (DCs) co-cultured with parasitized red blood cells (pRBCs). Moreover, both the number of CD4(+)CD25(+) regulatory T cells (Tregs) and the levels of IL-10 secreted by Tregs were reduced by pre-treatment with lentinan in the spleen of malaria-infected mice. Meanwhile, apoptosis of CD4(+) T cell in spleens of mice pretreated with lentinan was significantly reduced. In summary, lentinan can induce protective Th1 immune responses to control the proliferation of malaria parasites during the blood-stage of P.y17XL infection by stimulating maturation of DCs to inhibit negative regulation of the Th1 immune response by Tregs. Taken together, our findings suggest that lentinan has prophylactic potential for the treatment of malaria.
Article
beta-glucans are pharmacologic agents that rapidly enhance host resistance to a variety of biologic insults through mechanisms involving macrophage activation. To determine whether stimulation of the beta-glucan receptors on human monocytes resulted in cytokine production, monolayers of monocytes were incubated with purified yeast glucan particles and measured for tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) mRNA and protein. By Northern blot analysis, TNF-alpha mRNA was detected within 30 min of incubation with glucan particles, peaked at 2 h, and remained elevated for at least 8 h. Glucan induction of IL-1 beta mRNA followed a similar time-course of initiation and accumulation. By enzyme-linked immunosorbent assays (ELISAs), significant levels of TNF-alpha and IL-1 beta were present in supernatants of glucan-treated cells within 1 h and plateau levels of both cytokines were approached within 4 h. At particle-to-cell ratios of from 0.4 to 18, glucan particles induced dose-dependent increases in TNF-alpha and IL-1 beta mRNA and corresponding increases in TNF-alpha and IL-1 beta proteins. Exposure of monocytes to glucan particles for 0-30 min and washing before continued incubation for 4 h in particle-free buffer induced production and secretion of TNF-alpha and IL-1 beta in a time-dependent fashion compatible with phagocytosis. The pretreatment of monocyte monolayers with trypsin reduced glucan-induced production of TNF-alpha and IL-1 beta in a dose-dependent manner with 5 micrograms/ml of trypsin effecting reductions of greater than 50%. Thus, glucan particles induce human monocyte production of TNF-alpha and IL-1 beta by a mechanism that is dependent on trypsin-sensitive beta-glucan receptors.
Article
IL-10, a newly designated cytokine primarily produced by the Th2 subset of CD4+ T lymphocytes and Ly-1+ B lymphocytes, has recently been hypothesized to inhibit cytokine production by Th1 T cell clones by blocking accessory cell- (AC) dependent costimulatory function. To evaluate the effect of IL-10 on Con A-induced proliferative responses of resting murine T cells, purified T cells were cultured with different types of AC. The addition of IL-10 produced a 70 to 90% inhibition of resting T lymphocyte proliferation when purified populations of macrophages were used as AC, but had no effect on the AC function of T-depleted spleen cells, activated B cells, dendritic cells, or L cells. The inhibitory effects of IL-10 were inversely related to the concentration of mitogen and could be reversed by the addition of the neutralizing anti-IL-10 mAb, SXC1. The inhibition of macrophage AC function was not related to the induction of a suppressor cytokine as stimulation by mixtures of macrophages and limiting numbers of dendritic cells was not inhibited. The decrease in proliferative responses was primarily secondary to inhibition of IL-2 production although the failure of exogenous IL-2 to completely reconstitute the response suggested that IL-10 may also exert inhibitory effects on the induction of expression of a functional IL-2R. These results are most consistent with a model in which IL-10 inhibits the induction of expression on macrophages of a critical costimulatory molecule that may be constitutively expressed on other types of AC.
Article
A panel of antigen-specific mouse helper T cell clones was characterized according to patterns of lymphokine activity production, and two types of T cell were distinguished. Type 1 T helper cells (TH1) produced IL 2, interferon-gamma, GM-CSF, and IL 3 in response to antigen + presenting cells or to Con A, whereas type 2 helper T cells (TH2) produced IL 3, BSF1, and two other activities unique to the TH2 subset, a mast cell growth factor distinct from IL 3 and a T cell growth factor distinct from IL 2. Clones representing each type of T cell were characterized, and the pattern of lymphokine activities was consistent within each set. The secreted proteins induced by Con A were analyzed by biosynthetic labeling and SDS gel electrophoresis, and significant differences were seen between the two groups of T cell line. Both types of T cell grew in response to alternating cycles of antigen stimulation, followed by growth in IL 2-containing medium. Examples of both types of T cell were also specific for or restricted by the I region of the MHC, and the surface marker phenotype of the majority of both types was Ly-1+, Lyt-2-, L3T4+, Both types of helper T cell could provide help for B cells, but the nature of the help differed. TH1 cells were found among examples of T cell clones specific for chicken RBC and mouse alloantigens. TH2 cells were found among clones specific for mouse alloantigens, fowl gamma-globulin, and KLH. The relationship between these two types of T cells and previously described subsets of T helper cells is discussed.
Article
We investigated the effect of a fungal component, soluble beta-glucan, on secretory functions of murine alveolar macrophages (AMs) in vitro. Stimulation by beta-glucan (500 microg/mL) or interferon-gamma (IFN-gamma; 100 U/mL) alone had a slight effect on AM functions, but when AMs were incubated together with beta-glucan and IFN-gamma, the production and secretion of some immune mediators, such as nitric oxide, interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-alpha), were markedly augmented. This combined effect of beta-glucan and IFN-gamma was based on a priming effect of IFN-gamma, because prestimulation with IFN-gamma followed by beta-glucan induced high nitric oxide production of AMs, but reversal of the sequence of treatments had only a slight effect. We also found that preincubation of AMs with IFN-gamma enhanced the binding of fluorescein-labeled beta-glucan on the AM surface, and this increased binding was abrogated to the control level by the addition of three species of soluble unlabeled (1-->3)-beta-D-glucans but not by soluble alpha-glucan. These data imply that the priming effect of IFN-gamma on the AM response to beta-glucan was dependent, at least in part, on the enhancement of beta-glucan specific binding sites on the AM surface. It was suggested that IFN-gamma is one of the principal factors controlling the pulmonary immune system against both severe fungal infection and inflammation via AM activation at the alveoli.
Article
Changes in symptoms and airway responsiveness among persons who worked in a day-care center that had microbial growth problems were assessed before and after renovation. Before and after the building renovation, the investigators used the Limulus assay with (1-->3)-beta-D-glucan-specific lysate to measure airborne levels of (1-->3)-beta-D-glucan, a cell-wall component of molds. Airway responsiveness and subjective symptoms were measured among 14 female employees with a methacholine test and a standardized questionnaire. After the renovation, (1-->3)-beta-D-glucan-glucan levels decreased from 11.4 to 1.4 ng/m3. The number of persons who had increased airway responsiveness decreased after the renovation. Two employees developed a classical allergy to cat and pollen during the observation period. Although the study included only a few subjects and was based on only one day-care center, the data suggest that (1-->3)-beta-D-glucan may be related to airways inflammation caused by indoor air pollution.
Article
It has become widely accepted in the past decade that Th1 and Th2 cells represent alternate states of function and gene expression of CD41 T cells (Mosmann and Coffman 1989; Abbas et al. 1996). A question central to understanding the relevance of these subsets is whether they are products of an irreversible differentiation process or whether Th1 and Th2 cytokine patterns can be interchanged in an ordered or a regulated manner. Many disease states can be attributed to the activity of one specific Th subset, such as Th1-mediated autoimmune diseases or Th2-mediated allergic diseases and this implies that the ability to alter or reverse Th differentiation is a potential strategy for the treatment of such diseases.
Article
In studies on the relation between indoor mold exposure and symptoms/disease, the exposure should be described in terms of biomass and not viability. This paper reviews field studies in which (1--> 3)-ss-d-glucan was measured as a marker of biomass and was related to the extent of symptoms and measures of inflammation among exposed subjects. Increased levels of (1-->3)-ss-d-glucan were related to an increased extent of symptoms and markers of inflammation. The data suggest that (1-->3)-ss-d-glucan can be used as a risk marker in indoor environments.
Article
Exposure to organic dusts may cause airways inflammation in a large proportion of exposed persons. Most studies have relied on questionnaires and spirometry for diagnosis. To assess the possibility of determining the presence of inflammation using clinical diagnostic procedures, a study was undertaken among workers in a paper industry. Participants were 83 workers and 44 controls. Airborne endotoxin and (1-->3)-beta-D-glucan levels at the worksites were determined. The effects of this exposure were evaluated using a questionnaire, spirometry and measurements of airway responsiveness (methacholine) and levels of eosinophil cationic protein (ECP), myeloperoxidase (MPO), and C-reactive protein (CRP) in serum. The workers had a decreased baseline forced expiratory volume in one second (FEV1) and an increased airway responsiveness compared with controls. The concentrations of ECP and MPO were elevated compared with controls. There was a relation between exposure to endotoxin and (1-->3)-beta-D-glucan and airway responsiveness as well as ECP levels, when controlling for age, sex, smoking habits, atopy and asthma. The results suggest an increased prevalence of subjective respiratory symptoms, and an increased airway responsiveness among exposed workers. There was also a relationship between the serum concentration of eosinophil cationic protein and airway responsiveness. Taken together, the results suggest the presence of airways inflammation in the workers.
Article
(1-->3)-beta-D-glucan is a polyglucose structure in the cell wall of moulds, some bacteria and plants. Due to its unique (1-->3)-beta linkage it binds to specific receptors on phagocytosing cells and induces changes in their metabolism. Under realistic environmental concentrations, available data suggest that these changes express themselves as alterations of the defense mechanisms to other agents. Inhalation of (1-->3)-beta-D-glucan in humans causes symptoms from the upper respiratory tract and induction of cytokines in blood monocytes. (1-->3)-beta-D-glucan can be used as a marker of mould biomass in field studies. Relationships between the amount of (1-->3)-beta-D-glucan and the extent of symptoms as well as lung function changes and inflammatory markers have been described. In view of the mechanisms involved in the normal development of the immune system, children seem to be a particular group at risk due to (1-->3)-beta-D-glucan exposure.
Article
the study by Xu and colleagues, one of the current articles in focus (Ref. [30a][1], see [p. L527][2] in this issue), addresses the potential role of epithelial cell production of transforming growth factor (TGF)-β on fibrosis using immune cell-depleted lung tissue slices. This question is
Article
Beta-glucan has been shown to enhance anti-tumor and anti-infection functions in animals. Pigs at 4 months of age were infected with porcine reproductive and respiratory syndrome virus (PRRSV), and peripheral blood monocytes (PBMC) were isolated for the detection of interferon gamma (IFNgamma)-producing cells. We found that soluble high molecular weight beta-glucan could increase IFNgamma-producing cell frequency in a dose-dependent manner in the enzyme-linked immunospot assay (ELISPOT) in the absence of antigenic restimulation. A concentration as low as 1.6 microg/ml gave a significant increase and a similarly high enhancement was achieved at concentrations from 3.2 to 100 microg/ml. In PRRSV-specific IFNgamma ELISPOT, soluble beta-glucan elicited increased PRRSV-specific responses at concentrations from 3.2 to 50 microg/ml, but not at 100 microg/ml, whereas insoluble beta-glucan had no effect. Soluble beta-glucan augmented the porcine cellular immune response in an antigen-independent fashion, whereas insoluble beta-glucan had no activity. This finding suggests that soluble beta-glucan may enhance innate antiviral immunity against PRRSV.
Article
beta-(1-->3)-D-Glucan is an integral cell wall component of a variety of fungi, plants, and bacteria. Like the prototypic inflammatory mediator lipopolysaccharide (LPS), some beta-(1--> 3)-D-glucan-containing preparations have been shown to induce the production of proinflammatory cytokines by macrophages. In the present study, we have tested a new microparticulate form of beta-(1--> 3)-D-glucan (MG) from Saccharomyces cerevisiae for its ability to induce proinflammatory cytokine secretion in mouse peritoneal macrophages in vitro, and we have examined the effect of IFN-gamma. MG was rapidly phagocytized by peritoneal macrophages, and these MG-treated macrophages upregulated TNF-alpha, IL-6, and IL-1beta mRNAs and secreted these proinflammatory cytokines. IFN-gamma treatment alone did not induce unstimulated macrophages to produce TNF-alpha. However, a 4 h IFN-gamma pretreatment augmented TNF-alpha secretion by peritoneal macrophages subsequently treated with an optimally stimulatory dose of MG. IFN-gamma pretreatment for 2 h followed by thorough washing and a further 2 h incubation without IFN-gamma still resulted in enhanced TNF-alpha production in response to MG, suggesting that IFN-gamma can prime macrophages for a subsequent proinflammatory response. Most interestingly, we found that IFN-gamma pretreatment of peritoneal macrophages enhanced the TNF-alpha response to amounts of MG that were poorly stimulatory or non-stimulatory in the absence of IFN-gamma priming. These data suggest that a synergy between IFN-gamma and beta-glucan may have evolved to lower the threshold of sensitivity of the innate immune response to fungal pathogens.
Article
There have been a number of reports showing that the crude beta-glucan fraction prepared from various kinds of Basidiomycetes mushrooms acts as anti-cancer and anti-allergic reagent through stimulation of IFN-gamma production. It has been reported, however, that the exposure of the airway to beta-(1,3) d-glucan, contained in house dust, indoor moulds and some bacteria, potentiates the airway allergic response. It seems likely that the discrepant effects on immune function may be related to such factors as differences of the administration route, average molecular weight and water solubility. We isolated a new low-molecular-weight (about 100 kDa) beta-glucan from Aureobasidium pullulans 1A1 strain of black yeast, and found that it had low viscosity and was water-soluble. In this study, we examined the effects of water-soluble low-molecular-weight beta-(1-->3) and 50-80% branched beta-(1-->6) glucan (LMW-beta-Glucan) isolated from A. pullulans on the ova-albumin (OVA)-treated allergic reaction in mice. Feeding standard laboratory diets containing 0.5 and 1% LMW-beta-Glucan significantly inhibited the OVA-specific IgE elevation compared to that in OVA-sensitized mice fed standard laboratory diet alone (control). Furthermore, feeding standard laboratory diets containing 0.5 and 1% LMW-beta-Glucan inhibited the reduction of IL-12 and IFN-gamma production from splenocytes and the reduction of CD8- and IFN-gamma-positive cell number in the small intestine of the OVA-sensitized mice. These findings suggest that anti-food allergic action of LMW-beta-Glucan may be due to the inducing IFN-gamma production in the small intestine and splenocytes.
Article
The therapeutic benefits of fungal beta-glucans have been demonstrated as immuno-stimulating agents. In this study, we aimed to explore the mechanisms used by yeast beta-glucan-rich particles to activate murine resident macrophages for cytokine secretion. We demonstrated that resident macrophages were effectively activated by whole yeast beta-glucan particles (WGPs), such as with the upregulation of co-stimulatory molecules and the secretion of cytokines. The binding ability of WGPs and the levels of cytokine secretion in resident macrophages were significantly inhibited by soluble yeast beta-glucan but not by blockade of zymosan glucan receptor dectin-1. In addition, WGP-stimulated cytokine secretion was partially dependent on the MyD-88 pathway but was not significantly affected in CR3-deficient (CR3(-/-)) mice. Furthermore, we showed that Syk kinase was recruited upon WGP stimulation and was required for the production of cytokines. Taken together, these observations suggest that beta-glucan recognition is necessary but not sufficient to induce inflammatory response on resident macrophages. In addition, beta-glucan particles may use differential mechanisms for cytokine secretion in resident macrophages that may modulate both innate and adaptive immunity.
Article
Interleukin-10 (IL-10) is a cytokine with broad anti-inflammatory properties by its suppression of both macrophage and dendritic cell function, including antigen-presenting cell function and the production of proinflammatory cytokines. This can result subsequently in the feedback regulation of both T-helper 1 (Th1)-type and Th2-type responses. This review discusses the potential use of IL-10 or agents that induce IL-10 as potential anti-inflammatory therapies in inflammatory diseases. Although IL-10-deficient mice develop colitis in the presence of normal gut flora and clear certain intracellular pathogens more efficiently, this is often accompanied by immunopathology, which can be lethal to the host. This reinforces the anti-inflammatory properties of IL-10, although it should be noted that as discussed below, IL-10 can also promote B-cell and other immune responses under particular settings. A penalty of its role to limit the immune and inflammatory responses to pathogens and prevent damage to the host is that high or dysregulated levels of IL-10 may result in chronic infection. Thus, antagonists of IL-10 show great potential as adjuvants in preventative or therapeutic vaccines against chronic infection or cancer. This article reviews basic published studies on IL-10, which may lead to potential uses of IL-10 or its antagonists in human disease.
-3)-beta-D-glucan in buildings
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