IL-6 and TNFα are associated with depressive symptoms among men in a community-based cohort, with a tentative trend for IL-17A: Findings from the Shika Study in Japan.

OBJECTIVE: Emerging evidence suggests that low-grade systemic inflammation contributes to depressive symptoms; however, population-based longitudinal evidence, particularly from community samples, remains limited. This study examined the associations between serum cytokine levels and depressive symptoms among community-dwelling adults in Japan. PARTICIPANTS AND METHODS: Participants were drawn from the Shika Study cohort (N = 182; 98 men, 84 women; mean age: 62.2 ± 9.34 years for men, 60.9 ± 9.49 for women). They provided blood samples in 2017 and completed the Japanese versions of the Center for Epidemiologic Studies Depression Scale (CES-D) in 2017 and its revised version (CESD-R) in 2019. Serum TNFα, IL-6, IL-10 and IL-17A were quantified using a multiplex human immunoassay. RESULTS: Among men, serum IL-6 levels were positively associated with CES-D scores in 2017 after adjustment for age, visceral adiposity, smoking, and alcohol consumption (standardised regression coefficient (β) = 0.25, p = 0.024). Baseline TNF-α was significantly associated with higher CES-D-R scores in 2019 (β = 0.23, p = 0.026), whereas IL-17A showed only a non-significant trend (β = 0.13, p = 0.231). No significant associations were observed among women or for IL-10. CONCLUSION: In this exploratory community-based study, higher IL-6 levels were modestly associated with concurrent depressive symptoms in men, and baseline TNFα showed a similarly modest association with depressive symptoms two years later as measured by the CESD-R. IL-17A showed a tentative trend that requires replication. These findings suggest possible sex-specific links between peripheral inflammation and depressive symptoms, but the results should be interpreted as hypothesis generating.