Review
Stress Hormones, Th1/Th2 patterns, Pro/Anti-inflammatory Cytokines and Susceptibility to Disease

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Abstract

In general, stress has been regarded as immunosuppressive. Recent evidence, however, indicates that acute, subacute or chronic stress might suppress cellular immunity but boost humoral immunity. This is mediated by a differential effect of stress hormones, the glucocorticoids and catecholamines, on T helper 1 (Th1)/Th2 cells and type 1/type 2 cytokine production. Furthermore, acute stress might induce pro-inflammatory activities in certain tissues through neural activation of the peripheral corticotropin-releasing hormone–mast cell–histamine axis. Through the above mechanisms, stress might influence the onset and/or course of infectious, autoimmune/inflammatory, allergic and neoplastic diseases.

Section snippets

Role of Th1 and Th2 Cells and Type 1 and Type 2 Cytokines in the Regulation of Cellular and Humoral Immunity

Immune responses are regulated by antigen-presenting cells (APCs), such as monocytes/macrophages, dendritic cells and other phagocytic cells, which are components of innate immunity, and by the recently described T helper (Th) lymphocyte subclasses Th1 and Th2, which are components of acquired (adaptive) immunity5, 6 (Fig. 2). Th1 cells primarily secrete IFN-γ, IL-2 and TNF-β, which promote cellular immunity, whereas Th2 cells secrete a different set of cytokines, primarily IL-4, IL-10 and

Effects of Glucocorticoids

Previous studies have shown that glucocorticoids suppress the production of TNF-α, IFN-γ and IL-2 in vitro and in vivo in animals and humans1. As recently shown, glucocorticoids also act through their classic cytoplasmic/nuclear receptors on APCs to suppress the production of the main inducer of Th1 responses, IL-12, in vitro and ex vivo8, 9. Because IL-12 is extremely potent in enhancing IFN-γ and inhibiting IL-4 synthesis by T cells, the inhibition of IL-12 production might be a major

Further Complexities: the CRH–Mast Cell–Histamine Axis

Central, hypothalamic CRH might influence the immune system indirectly, through activation of the end products of the peripheral stress response, such as glucocorticoids and CAs. CRH, however, is also secreted peripherally at inflammatory sites (peripheral or immune CRH) and influences the immune system directly, through local modulatory actions1, 31. We identified immunoreactive CRH locally in: (1) experimental carrageenin-induced subcutaneous aseptic inflammation31; (2)

Infections

A major factor governing the outcome of infectious diseases is the selection of Th1- versus Th2-predominant adaptive responses during and after the initial invasion of the host. Thus, stress, and the consequent stress-induced Th2 shift, might have a profound effect on the susceptibility of the organism to infection and/or might influence the course of an infection, the defense against which is primarily through cellular immune mechanisms (Table 1).

Cellular immunity, particularly IL-12 and

Conclusions

Stress–immune system interactions are undoubtedly complex. Evidence accumulated over the past decade strongly suggests that stress hormones differentially regulate Th1/Th2 patterns and type 1/type 2 cytokine secretion. Although interest in the Th2 response was initially directed at its protective role in helminthic infections and its pathogenic role in allergy, this response might have important regulatory functions in countering the tissue-damaging effects of macrophages and Th1 cells5. Thus,

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