Role of corticosterone in immunosuppressive effects of acute ethanol exposure on Toll-like receptor mediated cytokine production.
Acute ethanol (EtOH) exposure causes a stress response in humans, nonhuman primates, and rodents. Previous study results indicate that the suppression of some immunological parameters by EtOH is mediated in part or completely by elevated corticosterone concentrations induced by EtOH. However, initial results suggested that corticosterone is not involved in the modulation of cytokine production by macrophages in response to polyinosinic polycytidylic acid (poly I:C). New studies were conducted to further evaluate the role of corticosterone in EtOH-mediated changes in production of interleukin-6 (IL-6), IL-10, and IL-12 in serum and peritoneal fluid in mice treated with poly I:C or lipopolysaccharide (LPS). Suppression of IL-6, but not IL-12, production by EtOH was found to be mediated by corticosterone. However, poly I:C, LPS, and EtOH all caused similar elevations of corticosterone concentrations; thus, it is not clear if EtOH is required to induce levels or durations of corticosterone needed to mediate the observed effects. The situation with IL-10 was more complicated. Inhibition of corticosterone synthesis with aminoglutethimide prevented the increase in IL-10 production caused by EtOH plus poly I:C as compared to poly I:C only. This indicates that this increase is dependent on corticosterone, but exogenous corticosterone plus poly I:C did not increase IL-10 production. Thus, EtOH and corticosterone are required. However, with LPS inhibition of corticosterone synthesis (using aminoglutethimide) or inhibition of its action (using mifepristone) further increased, or did not affect IL-10 concentrations, suggesting fundamental differences in the signaling pathways leading from poly I:C and LPS to IL-10 production.
Glover
Mitzi
M
Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, LSUHSC-S, 1501 Kings Highway, Shreveport, LA 71130, USA.
Pruett
Stephen B
SB
D000428:Alcohol Drinking / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D003345:Corticosterone / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis*; D000431:Ethanol / Q000008:administration & dosage* / Q000633:toxicity; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000633:toxicity; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013997:Time Factors; D051193:Toll-Like Receptors / Q000502:physiology*
D016207:Cytokines; D007166:Immunosuppressive Agents; D051193:Toll-Like Receptors; D000431:Ethanol; D003345:Corticosterone