Interleukin-6 moderates the relationship between social support, strain, and future depressive symptoms.

Background: Inflammation has been increasingly implicated in major depressive disorder (MDD), with interleukin-6 (IL-6) emerging as a key biomarker. How this relates to psychosocial risk factors, such as social support and strain, remains underexplored. IL-6 levels, social support, and strain may interact through shared underlying mechanisms in conferring depression risk. The study examined whether IL-6 levels moderate the associations between social support and strain with future MDD symptoms. Methods: Longitudinal data from 1,054 community adults in the Midlife Development in the United States (MIDUS) study were analyzed. Multiple linear regression models examined the main and interactive effects of social support, social strain, and IL-6 on future MDD symptoms. Serum IL-6 levels were measured using both enzyme-linked immunosorbent assay (ELISA) and Meso Scale Discovery (MSD) immunoassays, with results cross-examined. Sensitivity analyses, including generalized additive models (GAM) and covariate-adjusted models, were conducted to account for potential nonlinearities and confounders. Results: Lower social support and greater social strain predicted higher future MDD symptoms, particularly among individuals with elevated IL-6 levels. The interaction between social strain and IL-6 levels was robust across both ELISA ( Conclusion: IL-6 levels may moderate the relationship between social support, strain, and future MDD symptoms. Interpersonally-focused interventions enhancing social support or mitigating strain may consider the potential interacting role of inflammation in alleviating the psychosocial risk of depression.