Stress-induced suppression of in vivo splenic cytokine production in the rat by neural and hormonal mechanisms.
The mechanisms mediating the effects of stress on immune function have yet to be fully described. In vitro studies have demonstrated a role for both the sympathetic nervous system (SNS) and the hypothalamic pituitary adrenal axis (HPAA) in regulating immune responses following exposure to various stressors. The purpose of the present set of experiments was to determine the in vivo contribution of the HPAA and SNS in regulating the effects of stress on lipopolysaccharide (LPS) induced splenic cytokine production. For this, rats with combinations of sham surgeries, splenic nerve cuts (SNC), and adrenalectomies (ADX) were exposed to 15 min of 1.6 mA intermittent footshock immediately following the intravenous (i.v.) injection of 0.1 microg of LPS. Although footshock was immunosuppressive to most indices of cytokine production, neither SNC nor ADX alone blocked the effects of stress on splenic immune function. However the combination of these two manipulations significantly abrogated the immunosuppressive effects of stress on cytokine production. Adrenal demedullation of animals with a SNC demonstrated that the SNS, not the HPAA, was primarily responsible for the immunosuppressive effects of stress.
Meltzer
Jonathan C
JC
National Research Council of Canada Institute for Biodiagnostics, Winnipeg, MB, Canada R3E 0W3.
MacNeil
Brian J
BJ
Sanders
Veronica
V
Pylypas
Susan
S
Jansen
Arno H
AH
Greenberg
Arnold H
AH
Nance
Dwight M
DM
D000315:Adrenalectomy; D000704:Analysis of Variance; D000818:Animals; D016207:Cytokines / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D003714:Denervation; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000276:immunology; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D015213:Neuroimmunomodulation / Q000187:drug effects*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000294:innervation / Q000378:metabolism; D013315:Stress, Psychological / Q000276:immunology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000276:immunology* / Q000601:surgery; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000187:drug effects / Q000276:immunology
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha