Stress-Induced Immune Dysregulation: Implications for Wound Healing, Infectious Disease and Cancer

Institute for Behavioral Medicine Research, Ohio State University, Columbus, OH, USA.
Journal of Neuroimmune Pharmacology (Impact Factor: 4.11). 01/2007; 1(4):421-7. DOI: 10.1007/s11481-006-9036-0
Source: PubMed


The communication between the central nervous system and the immune system occurs via a complex network of bidirectional signals linking the nervous, endocrine and immune systems. The field of psychoneuroimmunology (PNI) has provided new insights to help understand the pathophysiological processes that are linked to the immune system. Work in this field has established that psychological stress disrupts the functional interaction between the nervous and immune systems. Stress-induced immune dysregulation has been shown to be significant enough to result in health consequences, including reducing the immune response to vaccines, slowing wound healing, reactivating latent herpesviruses, such as Epstein-Barr virus (EBV), and enhancing the risk for more severe infectious disease. Chronic stress/depression can increase the peripheral production of proinflammatory cytokines, such as interleukin (IL)-6. High serum levels of IL-6 have been linked to risks for several conditions, such as cardiovascular disease, type 2 diabetes, mental health complications, and some cancers. This overview will discuss the evidence that psychological stress promotes immune dysfunction that negatively impacts human health.

Download full-text


Available from: Jonathan Godbout, Apr 21, 2015
    • "In spite of the fact that stress response is a physiological protective phenomenon, like inflammatory response, it can also have detrimental effects on the organism [6]. Stress response has been found to be able to generate a wide range of problems ranging from impairment of wound healing to even cancer [6] [7]. The World Health Organization (WHO) estimated that mental diseases, including stress-related disorders, will be the second leading cause of disabilities by the year 2020 [8]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Noise is a psychological, environmental stressor that activates limbic sites in the brain. Limbic sites such as the amygdala and the amygdaloid corticotropin-releasing hormone (CRH) system play an important role in integrating stress response. We investigated the association between noise exposures, CRH-related molecules in the amygdala, and behavioral alterations. In total 54 Sprague-Dawley rats were divided into the following three groups: Control (CON), acute noise exposure (ANE), and chronic noise exposure (CNE). The ANE group was exposed to 100 dB white noise only once in 4 h and the CNE group was exposed to the same for 4 h per day for 30 days. Expression profiles of CRH and its receptors CRH-R1 and CRH-R2 were analyzed by quantitative real-time polymerase chain reaction (qPCR). The same stress procedure was applied to the ANE and CNE groups for behavior testing. The anxiety responses of the animals after acute and chronic stress exposure were measured in the defensive withdrawal test. CNE upregulated CRH and CRH-R1 mRNA levels but downregulated CRH-R2 mRNA levels. ANE led to a decrease in both CRH-R1 and CRH-R2 expression. In the defensive withdrawal test, while the ANE increased, CNE reduced anxiety-like behaviors. The present study shows that the exposure of rats to white noise (100 dB) leads to behavioral alterations and molecule-specific changes in the CRH system. Behavioral alterations can be related to these molecular changes in the amygdala.
    Noise and Health 05/2015; 17(76):141-147. DOI:10.4103/1463-1741.155838 · 1.48 Impact Factor
  • Source
    • "The most important rendering of nano-CaP therapy observed in the present study was improvement of neurotransmitters content in thigh muscle because novel neurological aspects of tumors were more elucidated and many evidences have further shown that tumors growth process is also related to the nervous system. More important, numerous neurotransmitters influence tumor vascularization and cell migration [31]; in addition, they may also suppress the immune response in cancer [32]. These influences are increased by the ability of the cancer cells to secret neurogenic factors [33], which influences neurons development. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The present study aimed to investigate the mode of action of nano-CaPs in vivo as a therapy for solid tumor in mice. To achieve this goal, Ehrlich Ascites Carcinoma (EAC) was transplanted into 85 Swiss male albino mice. After nine days, the mice were divided into 9 groups. Group 1 and 2 were allocated as the EAC control. Group 3 and 4 were injected once intratumorally (IT) by nano-calcium phosphate (nano-CaP). Group 5 and 6 were received once intraperitoneal injection (IP) of nano-CaP. Group 7, 8, and 9 were received nano- CaP (IP) weekly. Blood samples and thigh skeletal muscle were collected after three weeks from group 1, 3, 5, and 7 and after four weeks from group 2, 4, 6, and 8. On the other hand, group 9 received nano-CaP (IP) for four weeks and lasted for three months to follow up the recurrence of tumor and to ensure the safety of muscle by histopathological analysis. Tumor growth was monitored twice a week throughout the experiment. DNA fragmentation of tumor cells was evaluated. In thigh tissue, noradrenaline, dopamine, serotonin (5HT), and gamma-aminobutyric acid (GABA) were measured. In serum, 8-Hydroxy-deoxyguanosin (8-OHDG), adenosine triphosphate (ATP), and vascular endothelial growth factor (VEGF) were analyzed. Histopathological and biochemical results showed a significant therapeutic effect of nano-CaP on implanted solid tumor and this effect was more pronounced in the animals treated IP for four weeks. This improvement was evident from the repair of fragmented DNA, the significant decrease of caspase-3, 8-OHDG, myosin, and VEGF, and the significant increase of neurotransmitters (NA, DA, 5HT, and GABA). Additionally, histopathological examination showed complete recovery of cancer cells in the thigh muscle after three months.
    Journal of Advanced Research 04/2015; 103. DOI:10.1016/j.jare.2015.04.001
  • Source
    • "Gene set enrichment analysis of these 123 genes revealed that, compared to controls, anxious men had altered gene expression in biological pathways involving immune responses to acute viral or bacterial infection, as well as to influenza vaccination in a variety of immune cells, including monocytes, macrophages, myeloid dendritic cells, B cells, neutrophils, and mast cells. As mentioned earlier, clinical and epidemiological studies found that anxiety has a negative impact on immune functions (Godbout and Glaser, 2006; Arranz et al., 2007) as reflected by reduced immune response to vaccinations (Miller et al., 2004; Vedhara et al., 1999; Glaser et al., 1992; Morag et al., 1999; Burns et al., 2002), reactivation of latent herpes virus (Cohen et al., 1999), and increasing risk of infectious diseases (Sareen et al., 2005; Cohen et al., 1991). Our results are consistent with these epidemiological findings and shed some light on the molecular pathways in various immune cells by which anxiety can affect immune functioning. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Prospective epidemiological studies found that generalized anxiety disorder (GAD) can impair immune function and increase risk for cardiovascular disease or events. Mechanisms underlying the physiological reverberations of anxiety, however, are still elusive. Hence, we aimed to investigate molecular processes mediating effects of anxiety on physical health using blood gene expression profiles of 336 community participants (157 anxious and 179 control). We examined genome-wide differential gene expression in anxiety, as well as associations between nine major modules of co-regulated transcripts in blood gene expression and anxiety. No significant differential expression was observed in women, but 631 genes were differentially expressed between anxious and control men at the false discovery rate of 0.1 after controlling for age, body mass index, race, and batch effect. Gene set enrichment analysis (GSEA) revealed that genes with altered expression levels in anxious men were involved in response of various immune cells to vaccination and to acute viral and bacterial infection, and in a metabolic network affecting traits of metabolic syndrome. Further, we found one set of 260 co-regulated genes to be significantly associated with anxiety in men after controlling for the relevant covariates, and demonstrate its equivalence to a component of the stress-related conserved transcriptional response to adversity profile. Taken together, our results suggest potential molecular pathways that can explain negative effects of GAD observed in epidemiological studies. Remarkably, even mild anxiety, which most of our participants had, was associated with observable changes in immune-related gene expression levels. Our findings generate hypotheses and provide incremental insights into molecular mechanisms mediating negative physiological effects of GAD.
    Brain Behavior and Immunity 10/2014; 43. DOI:10.1016/j.bbi.2014.09.016 · 5.89 Impact Factor
Show more