Alcohol consumption attenuates febrile responses to lipopolysaccharide and interleukin-1β in male rats

Background: Chronic and acute alcohol use exert profound modulatory effects on the immune system which manifest as impaired host defense against infections. An important feature of this response is the interaction between the immune and the central nervous systems. This study investigated the effects of 14 days of alcohol exposure on cytokine-mediated neuroimmune interactions that affect the febrile component of the host-defense response. Methods: Adult male rats were fed a liquid diet containing ethanol (EtOH, 5% w/v) for 14 days. Pair-fed and normal chow- and water-fed rats served as controls. Continuous biotelemetric recordings of body temperature and locomotor activity commencing after 14 days of EtOH feeding were used to determine the effects of chronic EtOH on the circadian pattern of temperature and activity, on the febrile response to intraperitoneal (ip) administration of lipopolysaccharide (LPS) and interleukin (IL)-1β, and on fever induced by IL-1β administered intracerebroventricularly. We also examined the effects of EtOH consumption on LPS-induced hypothalamic production of the pyrogenic cytokines IL-1β and tumor necrosis factor-α (TNFα) and on the blood levels of IL-1β, TNFα, IL-6, adrenocorticotropin, and corticosterone at 2, 4, and 6 hr after ip LPS. Results: Fourteen days of EtOH consumption blunted the circadian increases in temperature and activity that normally occur in the dark phase of the light/dark cycle without affecting light-phase temperature or activity. EtOH consumption attenuated fever induced by LPS or IL-1β administered ip during the light phase and significantly reduced hypothalamic production of IL-1β. LPS-induced increases in hypothalamic TNFα and blood cytokines, adrenocorticotropin, and corticosterone were unaffected. Central administration of IL-1β produced a normal febrile response in chronic-EtOH rats. Conclusions: The attenuated LPS- and IL-1β - induced febrile responses in EtOH-consuming rats and the corresponding deficit in hypothalamic production of IL-1β suggest that alcohol may impair IL-1β - mediated neuroimmune communication.