Purpose: Inflammation has been shown to underlie the pathogenesis of osteoarthritis. We evaluated the association between inflammatory biomarkers in peripheral blood and severity of knee osteoarthritis (KOA). Methods: We performed a cross-sectional study of 139 participants with frequent knee pain, evaluated radiographic severity according to the Kellgren-Lawrence (KL) grading, joint space narrowing (JSN) and osteophyte (OST) formation, and clinical severity according to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). We measured five inflammatory markers: plasma (p) IL-1Ra, IL-1b, IL-18, serum (s) CD14, hsCRP and five bone and cartilage biomarkers urine (u) CTX-II, (s) HA, COMP, CTX-I, PIIANP. Associations between various biomarkers with severity of KOA were evaluated, with and without adjustment for age, gender and body mass index (BMI). Results: (p) IL-1Ra was negatively associated with radiographic severity assessed by KL of index knee (Spearman rho (r)¼-0.197, P¼ 0.021), OST of index knee (r¼-0.217, P¼ 0.011), JSN of index knee (r¼-0.172, P¼ 0.045) and KL sum score of both knees (r¼-0.180, P¼ 0.035), after adjustment for age, gender and BMI. Other inflammatory biomarkers were not associated with radiographic severity after adjustment. The cartilage degradation markers (u) CTXII and (s) COMP were modestly associated with radiographic severity after adjustment. In multivariate models, (s) hsCRP and the bone and cartilage biomarkers, but not the inflammatory biomarkers, were associated with radiographic severity. Conclusions: Among the inflammatory biomarkers in peripheral blood, IL-1Ra was negatively associated with radiographic severity of KOA. This supports the role of inflammation in the pathogenesis of OA, and these biomarkers are potential candidates for evaluation of their ability to prognosticate progression of KOA in longitudinal studies.
