Disease Activity Is More Associated with IL-1 Than with IL-6 in Patients with Rheumatoid Arthritis

Abstract

Interleukin-1 receptor antagonist (IL-1ra) concentration reflects and is proportional to IL-1 production. Both IL-1 and IL-6 are involved in the pathogenesis of rheumatoid arthritis (RA). However, the relationship of serum levels of these two cytokines to each other in RA patients is not well-understood. In this study, our objective was to analyze the possible linear correlation between IL-1ra and IL-6 in patients with RA, and how both are related to the inflammatory activity of the disease. IL-6 and IL-1ra levels were measured in 407 patients with RA. Linear regression and partial correlations were conducted to analyze the relationship between both cytokines, and their association with RA characteristics. No correlation was found between serum levels of IL-6 and IL-1ra (Pearson’s r 0.031, p = 0.61). However, disease activity and acute phase reactants were positively and significantly associated with both cytokines. Nevertheless, after controlling for covariates, disease activity scores were more strongly associated with IL-1ra compared to IL-6. Circulating IL-6 and IL-1ra do not correlate with each other in RA patients. Although both are associated with disease activity and acute phase reactants, the relationship of disease activity to IL-1ra is greater than that to IL-6.

Engineered Self-Regulating Macrophages for Targeted Anti-inflammatory Drug Delivery

“…However, there was a clear distinction between direct and indirect co-culture groups as well as low and high levels of IL-1β in co-culture in terms of therapeutic mitigation. Studies have demonstrated that production of IL-1Ra, a natural inhibitor of IL-1, is elevated in in ammatory RA joints [57]; however, the levels produced in RA joints are usually insu cient to reduce damage, as a concentration of 10-to-100-fold excess of IL-1Ra is required to effectively inhibit IL-1, which is a limiting factor for IL-1Ra as a clinical therapeutic [58]. Stimulation with 1 or 10 ng/mL IL-1β used in these experiments represent super-physiological levels as concentrations of IL-1β have been reported between 0.115 to 0.5 ng/mL in the synovial uid in early spontaneous joint degeneration [55].…”