Sex differences in inflammatory mechanisms related to alcohol use disorder and depression

Alcohol use disorder (AUD) continues to negatively impact millions of men and women in the United States each year, and current available treatments for AUD lack widespread efficacy. Major depressive disorder (MDD) is the most common comorbid condition with AUD and is also often treatment resistant. Many studies have found a relationship of immune modulators with both alcohol use and depression. There are many sex differences within the immune system that may contribute to both AUD and MDD, as well as to sex differences in their prevalence and presentation. Examining these mechanisms may offer more effective treatment options. The following review focuses on immune signaling mechanisms, including pattern recognition receptors and proinflammatory cytokines, which have been strongly associated with alcohol use and MDD. Within the context of these signaling systems, we will further discuss known sex differences in their function that may contribute to behavioral outcomes.