Stressed to death: Implication of lymphocyte apoptosis for psychoneuroimmunology
Introduction
The effect of physical and psychological stress on the immune system has been noticed since the 1940s (Kiecolt-Glaser, McGuire, Robles, & Glaser, 2002). Various studies with different model systems have demonstrated that depending on the mood and duration, stress could either enhance or reduce immune function (Ader & Cohen, 1993). It is generally accepted that acute stress could improve the function of the immune system, while chronic stress often results in reduction of immune responses (Dhabhar & McEwen, 1997). It has been shown that acute stress-promoted immune responses are dependent on the hypothalamic–pituitary–adrenal (HPA) axis (Dhabhar & McEwen, 1999), while the mechanisms by which chronic stress exerts its effect remain controversial. Our studies have shown that chronic restraint stress-induced lymphocyte reduction occurs through endogenous opioid-mediated Fas expression, which in turn induces apoptosis (Yin et al., 1999, Yin et al., 2000). In this paper we will briefly review lymphocyte apoptosis and its role in the regulation of lymphocyte homeostasis and immune responses. Our particular attention will be focused on chronic stress-induced lymphocyte apoptosis and the mechanisms controlling this process.
Section snippets
Apoptosis and lymphocyte homeostasis
Apoptosis is an evolutionary conserved ‘cell suicide’ program present in all nucleated metazoan cells (Chinnaiyan & Dixit, 1996; Meier, Finch, & Evan, 2000). Despite its highly conserved nature, it is only recently that any of the molecular mechanisms underlying apoptosis have been identified (Rich, Watson, & Wyllie, 1999). Apoptosis is now known as an active cell death process characterized by the activation of proteases, auto-destruction of chromatin, nuclear condensation, cellular membrane
Fas (CD95/APO-1) and Fas ligand (FasL/CD95L)
Fas antigen is a type I membrane protein of 45 kDa that belongs to the tumor necrosis factor (TNF)/nerve growth factor receptor family (Itoh et al., 1991). It is expressed on a variety of cell types including activated T- and B cells, hepatocytes, and ovarian epithelial cells (Watanabe-Fukunaga et al., 1992). It is also detected in solid tumors of the breast, ovary, colon, prostate, and liver. Ligation of this molecule with specific antibodies or its natural ligand (FasL) usually induces rapid
Opioids and immunosuppression
Opiates are an old class of drugs derived from the milky latex of poppy of the opium poppy Papaver somniferum and have been used for centuries as analgesics. Morphine is the primary alkaloid in opium. Opioids have effects on perception of pain, consciousness, motor control, mood, and autonomic function, and often induce physical dependence or addiction (Kieffer & Evans, 2002). In the mid 1970s, scientists discovered the existence of an endogenous morphine-like substance, enkephalin, in the
Lymphocyte apoptosis induced by chronic stress
Various studies have clearly demonstrated that the immune system is very sensitive to either physiological or psychological stress. Stress has been demonstrated in both humans and animals to be immunomodulatory and alter the pathogenesis of tumor development, autoimmunity, and infectious diseases by influencing the onset, course, and outcome of the pathological processes (Rabin, Cohen, Ganguli, Lysle, & Cunnick, 1989). Although acute stress is generally believed to exert positive effects on the
The mechanisms
Bi-directional communication between the nervous and immune systems occurs through neuroendocrine mechanisms and interaction with lymphoid tissue. It is clear that psychological or physical stressors that activate these pathways can alter immunity and disease resistance. Many mechanisms have been proposed to account for stress-induced alterations in immunity, including changes in the lymphocytes signaling process, migration pattern, and viability. We will review the literature regarding cell
Summary
Chronic stress often leads to the suppression of the immune system. In this paper, we have summarized current literature related to stress-induced lymphocyte apoptosis under stress conditions. Based on available knowledge, stress induced-lymphocyte apoptosis does may play a prominent role in the pathogenesis of various diseases. Increasing evidence suggests that a compromised immune system may be a major contributor to cancer development and can impact the outcome of cancer therapies. We
Acknowledgements
This work was supported by research grants AI50222 and AI43384 from the National Institute of Health and Grant IIH 00208 from the National Space Biomedical Research Institute.
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