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Neuroendocrine Regulation of IL‐12 and TNF‐α/IL‐10 Balance: Clinical Implications
Author(s) -
ELENKOV ILIA J.,
CHROUSOS GEORGE P.,
WILDER RONALD L.
Publication year - 2000
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2000.tb05374.x
Subject(s) - immune system , medicine , histamine , adenosine , tumor necrosis factor alpha , immunology , endocrinology , chronic stress , immunity
A bstract : Interleukin‐12 and tumor necrosis factor (TNF)‐α promote T‐helper (Th) 1 responses and cellular immunity, whereas IL‐10 suppresses Th1 activities and stimulates Th2 and humoral immune responses. Recent evidence indicates that glucocorticoids, norepinephrine, epinephrine, histamine, and adenosine inhibit the production of human IL‐12 and TNF‐α, whereas they do not affect or even stimulate the production of IL‐10. Through this mechanism these neuroendocrine mediators may cause a selective suppression of Th1 responses and a Th2 shift rather than generalized Th suppression. The substantial Th2‐driving force of endogenous stress mediators, as well as histamine and adenosine, can be amplified to a great extent during certain conditions and may play a role in increased susceptibility of the organism to various infections that are normally cleared by Th1 responses. In addition, conditions that contribute to a substantial increase or decrease of local or systemic concentrations of these mediators via modulation of IL‐12, TNFα/IL‐10 balance may also play a role in induction, expression, and progression of certain autoimmune diseases, allergic/atopic reactions, and tumor growth. These conditions include: acute or chronic stress; cessation of chronic stress or chronic hypoactivity of the stress system; severe exercise; serious surgical procedures or traumatic injuries; major burns; severe ischemia or hypoxia; pregnancy and the postpartum period. Thus, better understanding of the neuroendocrine regulation of IL‐12, TNF‐α/IL‐10 balance might help the development of new therapeutic strategies for the treatment of Th1‐ and Th2‐mediated human diseases.