title: The role of stress mediators in modulation of cytokine production by ethanol.
abstract: Acute ethanol exposure in humans and in animal models activates the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS); the resultant increases in concentration of neuroendocrine mediators contribute to some of the immunosuppressive effects of ethanol. However, the role of these mediators in the ethanol-induced inhibition of inflammatory responses is not clear. This is complicated by the fact that most inflammatory stimuli also activate the HPA axis and SNS, and it has not been determined if ethanol plus an inflammatory stimulus increases these stress responses. Addressing this issue is the major focus of the study described herein. Complementary approaches were used, including quantitative assessment of the stress response in mice treated with polyinosinic-polycytidylic acid (poly I:C, as an inflammatory stimulus) and inhibition of the production or action of key HPA axis and SNS mediators. Treatment of mice with ethanol shortly before treatment with poly I:C yielded a significant increase in the corticosterone response as compared to the response to poly I:C alone, but the increase was small and not likely sufficient to account for the anti-inflammatory effects of ethanol. Inhibition of catecholamine and glucocorticoid production by adrenalectomy, and inhibition of catecholamine action with a sustained release antagonist (nadalol) supported this conclusion and revealed that "excess" stress responses associated with ethanol treatment is not the mechanism of suppression of pro-inflammatory cytokine production, but stress-induced corticosterone does regulate production of several of these cytokines, which has not previously been reported.
authors.affiliation: LSU Health Sciences Center, Department of Cellular Biology and Anatomy, Shreveport, LA 71130, USA.
authors.forename: Mitzi
authors.initials: M
authors.lastname: Glover
authors.forename: Bing
authors.initials: B
authors.lastname: Cheng
authors.forename: Ruping
authors.initials: R
authors.lastname: Fan
authors.forename: Stephen
authors.initials: S
authors.lastname: Pruett
mesh_terms: D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000097:blood*; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009490:Neurosecretory Systems / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D013312:Stress, Physiological
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D000431:Ethanol; D011070:Poly I-C; D003345:Corticosterone