Sex differences in the relationship between individual systemic markers of inflammation and pain in knee osteoarthritis

Abstract

There are suggestions that the relationship between inflammation and pain in osteoarthritis (OA) may differ by sex, yet studies have been limited. We investigated whether the relationship between knee-specific OA pain and systemic inflammatory markers differs by sex. 196 patients scheduled for knee arthroplasty for OA were included. Questionnaires were completed and blood samples drawn pre-surgery. Questionnaire data: knee pain (WOMAC), sex, age, height, weight, comorbidities, depressive symptoms, and symptomatic joint count. Systemic inflammatory markers (cytokines IL-6, IL-8, IL-10, IL-1β and TNF-α) were measured by multiplex ELISA. A series of regression models with interaction terms between sex and ln-transformed inflammatory markers were estimated with pain score as the outcome. The adjusted relationship between pain and inflammatory markers, by sex, were presented graphically. Mean age was 64 years (range 43-89); females comprised 58.7% of the sample. In adjusted analyses, similar relationships between knee pain and lnIL-10 (negative: β​=​-1.28, 95%CI (-1.97, -0.58)) and lnTNF-α (positive: β​=​0.92, 95%CI (0.11, 1.76)) were found for females and males. In contrast, relationships between knee pain and lnIL-1β, lnIL-6 and lnIL-8 differed in direction for females and males. Specifically, for lnIL-1β and lnIL-8 they were positive for males, negative for females. The opposite was found with lnIL-6, negative for males, positive for females. These findings provide some evidence of sex-specific relationships between individual inflammatory markers and knee OA pain. They expose a need for further exploration of sex-differences in this context, with potential future implications for treatment or drug development in OA.