Interleukin‐6 is a significant predictor of radiographic knee osteoarthritis: The Chingford study

Abstract

ObjectiveThere is a great need for identification of biomarkers that could improve the prediction of early osteoarthritis (OA). We undertook this study to determine whether circulating levels of interleukin-6 (IL-6), tumor necrosis factor α (TNFα), and C-reactive protein (CRP) can serve as useful markers of radiographic knee OA (RKOA) in a normal human population.MethodsRKOA data were obtained from the cohort of the Chingford Study, a prospective population-based study of healthy, middle-aged British women. The RKOA-affected status of the subjects was assessed using the Kellgren/Lawrence (K/L) grade as determined on radiographs obtained at baseline (n = 908) and at 10 years and 15 years thereafter. Serum levels of CRP, IL-6, and TNFα were assayed at 5, 8, and 15 years, using high-sensitivity commercial assays. A K/L grade of ≥2 in either knee was used as the outcome measure. Statistical analyses included analysis of variance for repeated measurements and logistic regression models, together with longitudinal modeling of dichotomous responses.ResultsDuring 15 years of followup, the prevalence of RKOA (K/L grade ≥2) increased from 14.7% to 48.7% (P < 0.00001 versus baseline). The body mass index (BMI) and circulating levels of CRP and IL-6 were consistently and significantly higher in subjects diagnosed as having RKOA. When multiple logistic regression was applied to the data, the variables of older age (P = 3.93 × 10−5), higher BMI at baseline (P = 0.0003), and increased levels of IL-6 at year 5 (P = 0.0129) were determined to be independent predictors of the appearance of RKOA at year 10. The results were fully confirmed using longitudinal modeling of repeated measurements of the data obtained at 3 visits. The odds ratio for RKOA in subjects whose IL-6 levels were in the fourth quartile of increasing levels (versus the first quartile) was 2.74 (95% confidence interval 1.94–3.87).ConclusionThis followup study showed that individuals were more likely to be diagnosed as having RKOA if they had a higher BMI and increased circulating levels of IL-6. These results should stimulate more work on IL-6 as a potential therapeutic target.

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

“…2A), both of which are associated with OA inflammation. 65,66 At the protein level, however, only the increase in IL-6 (*366-fold; p = 0.002) expression was statistically significant (Fig. 2C).…”

Raised serum IL 6 and CRP in Radiographic Knee Osteoarthritis in Eastern India

“…Moreover, other cross-sectional studies also found their altered levels, especially those of CRP, are elevated in OA, although results in recent reports have been contradictory [1518] . The serum levels of IL-6 were associated with the change in knee pain over 5 years and with the future prevalence of radiological knee osteoarthritis (RKOA) [19,20] . The serum levels of IL-6 and hs-CRP were considered to be predictors of a decreased articular cartilage volume in patients with RKOA.…”

Expression of IL-1β Receptor Antagonist in Patients with Severe Osteoarthritis of the Knee–The Mechanism Limiting the Inflammation in Osteoarthritis

“…These results indicate the development of strong anti-catabolic response in patients from the OA group. Such direction of changes may prove to be characteristic of OA, in contrast to RA [27]. The mechanism of action of IL-1β and anti-catabolic response to this cytokine is associated with the activity of membrane IL-1β receptor, which expression is increased in chondrocytes and synovial cells of people with OA.…”