Neuroendocrine regulation of IL-12 and TNF-alpha/IL-10 balance. Clinical implications.
Interleukin-12 and tumor necrosis factor (TNF)-alpha 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-alpha, 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, TNF alpha/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-alpha/IL-10 balance might help the development of new therapeutic strategies for the treatment of Th1- and Th2-mediated human diseases.
Inflammatory Joint Diseases Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. elenkovi@mail.nih.gov
I J
IJ
Elenkov
G P
GP
Chrousos
R L
RL
Wilder
D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology*; D018664:Interleukin-12 / Q000502:physiology*; D015213:Neuroimmunomodulation; D009490:Neurosecretory Systems / Q000276:immunology*; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12