Association of the risk of osteoarthritis with high innate production of interleukin-1β and low innate production of interleukin-10 ex vivo, upon lipopolysaccharide stimulation

Objective. In a sibpair study of osteoarthritis (OA) patients, we investigated whether, upon stimulation with lipopolysaccharide (LPS), variations in the innate ex vivo production of interieukin-1 beta (IL-1 beta), IL-1 receptor antagonist (IL-1Ra), IL-10, and tumor necrosis factor a (TNF alpha) in whole-blood assays contribute to the risk of OA. Methods. Data from 305 patients with OA at multiple sites (hand, knee, hip, and spine), whose median age was 60 years (range 43-79 years), were compared with those from 137 controls. OA was defined in accordance with the American College of Rheumatology criteria. Whole-blood samples were stimulated with LPS (10 ng/ml). In the supernatants, cytokines were measured by enzyme-linked immunosorbent assay. Odds ratios (ORs) were used as measures of the relative risk of OA in relation to quartiles of IL-1 beta, IL-1Ra, TNFa, and IL-10 production. The ORs were adjusted for sex and age, and 95% confidence intervals (95% CIs) were computed using robust standard errors to take into account the intrafamily effect. Results. Subjects in the highest quartile of IL-1 beta and IL-1Ra had an increased risk of OA (OR 3.3, 95% CI 1.4-7.9 and OR 8.0, 95% CI 3.7-17.4, respectively), while subjects in the lowest quartile of IL-10 had a 3-fold increased risk of OA (OR 3.1, 95% CI 1.5-6.5). High innate ex vivo production of TNF alpha was not associated with an increased risk of OA. Conclusion. Subjects with a high innate ex vivo production of IL-1 beta and IL-1R alpha and low innate ex vivo production of IL-10 have an increased risk of OA. These results suggest that a proportion of the genetic susceptibility to OA may be encoded for by variations in innate cytokine activity.