Practical aspects of cytokine-determination in the synovial fluid of patients with osteoarthritis, rheumatoid arthritis and other joint-diseases

Objective To determine whether the activity of cartilage-degrading enzymes in the synovial fluid (SF) of patients with rheumatoid arthritis and other joint diseases is correlated with the concentration of cytokines in the SF. Methods Cytokines and cartilage-degrading enzymes were determined in the SF of 97 patients with various disorders involving the knee joints (rheumatoid arthritis (RA) n 44; osteoarthritis (OA) n 35; meniscal trauma (Men) n 10; reactive arthritides (ReA) n 8). In these samples we measured the concentrations of interleukin-1 alpha and beta, IL-1-receptor antagonist (IL-1ra), IL-6, IL-8, tumor necrosis factor alpha (TNF alpha; all by ELISA), collagenase-activity and caseinase-activity (by substrate assays). Results With the exception of IL-1 alpha and IL-6, cytokine-concentrations were significantly higher in RA than in OA SF-samples (p < 0.05; ANOVA on ranks). IL-1ra, IL-6, and IL-1 beta were correlated best with the collagenase-activity in the SF (r = 0.63; 0.57; 0.55; Spearman's rank correlation), while IL-1 beta (r = 0.53) and IL-1ra (r = 0.52) were best correlated with the caseinase-activity in the samples. The SF-concentration of IL-1ra was well correlated with the levels of IL-6, IL-1 beta, II-8, and TNF alpha (r from 0.73 to 0.66; all p < 0.005), but not with IL1 alpha. The molar ratio of IL-1 to IL-1ra in the SF was neither correlated with the activity of collagenase nor caseinase. IL-1 beta and IL-1ra in the SF were positively correlated with the erythrocyte sedimentation rate (ESR). Conclusions The determination of IL-1 beta and IL-1ra in the SF of patients with joint disorders as examined in this study seems to allow to a certain extent a prediction of the collagenase- and caseinase-activity contained in the diseased joint. We would favor the measurement of IL-1ra, since it was usually found in a more than 100-fold molar excess over IL-1 beta. The molar ratio of IL-1 to IL-1ra had no predictive value for the activity of cartilage-degrading enzymes in the sample, or for the patient's ESR. The hypothesis that in rheumatic diseases the IL-1/IL-1ra - ratio in the SF may reflect the inflammatory activity of the respective joint, is not supported by our data.