Inflammatory cytokine levels and depressive symptoms in older women in the year after hip fracture: Findings from the Baltimore hip studies

Objectives To determine whether interleukin (IL)-6 or soluble tumor necrosis factor alpha receptor 1 (sTNF-αR1) is associated with depressive symptoms in the year after hip fracture. Design Prospective cohort. Setting Three Baltimore-area hospitals. Participants Community-dwelling women aged 65 and older admitted with a new, nonpathological fracture of the proximal femur (N = 134). Measurements Two, 6, and 12 months after fracture, serum was analyzed for IL-6 and sTNF-αR1, and depressive symptoms were measured using the 15-item Geriatric Depression Scale (GDS). Generalized estimating equations were used to model the longitudinal relationship between IL-6, sTNF-αR1, and GDS score. Whether lower extremity function, as measured according to the Lower Extremity Gain Scale (LEGS), explained the relationship between IL-6, sTNF-αR1, and GDS score was also examined. Results Participants in the highest categories of IL-6 (≥5.14 pg/mL) and sTNF-αR1 (≥2,421 pg/mL) had the highest GDS scores in the year after fracture (P =.09 for both). Twelve months after fracture, those in the highest IL-6 and sTNF-αR1 categories had GDS scores that were on average 1.9 (95% confidence interval (CI) = 0.4-3.4, P =.01) and 1.4 (95% CI = -0.1-3.0, P =.07) points higher than those in the lowest category, respectively. Adjusting for LEGS score, the mean difference in GDS scores for highest versus lowest IL-6 categories was 1.6 (95% CI = 0.2-3.0, P =.02) points at 12 months. Conclusion Results from these exploratory analyses support a role for inflammation in the pathophysiology of depressive symptoms after hip fracture. Depressive symptoms in the context of high cytokine levels may represent a sickness syndrome that is chronic in some individuals. Further research should establish the cause and effect of this relationship, as well as long-term correlates.