Prolonged Drinking in the Dark in Adult Female Mice Attenuates the Central and Peripheral Cytokine Response to Lipopolysaccharide Academic Article uri icon

Abstract

  • Alcohol misuse has long-term effects on immune function, and can alter the inflammatory profile basally and following an insult. Additionally, alcohol-induced inflammation may promote alcohol cravings and dependence, suggesting a bidirectional relationship. However, most studies assessing the relationship between alcohol consumption and innate immune signaling were performed exclusively in males or yielded ambiguous results. The present study extended this work by assessing the bidirectional association between ethanol (EtOH) and inflammation in the Drinking in the Dark (DID) binge paradigm in adult females. A week after receiving LPS (1 mg/kg) or saline, female C57BL/6 J mice were evaluated for voluntary EtOH consumption in a prolonged DID paradigm. Next, whether prolonged voluntary EtOH intake influenced the inflammatory response to LPS in the brain and liver was assessed. Our results demonstrate that voluntary binge drinking in the DID model was unaltered by a prior immune challenge. However, prolonged EtOH consumption attenuated the central and peripheral immune response to LPS exposure. Compared to water-drinking females, EtOH-consuming females showed diminished brain levels of interleukin-1β (IL-1β) (p = 0.005), liver levels of IL-1β, and tumor necrosis factor-α four hours after LPS (p < 0.05). Twelve days of DID was not sufficient to promote a basal increase in inflammatory cytokines. Collectively, the results demonstrate that prolonged voluntary EtOH exposure blunts the proinflammatory innate immune response to a secondary immune challenge in adult females. These findings provide insight into the immunomodulatory effects of binge EtOH intake in females, extending our understanding of the role of inflammatory signaling in alcohol-consuming individuals.

Publication Date

  • 2025-05-01