The effect of IL-1β on the expression of inflammatory cytokines and their receptors in human chondrocytes

Abstract

Cytokines released at sites of inflammation and infection can alter the normal processes of cartilage turnover, resulting in pathologic destruction or formation. Interleukin (IL)-1β plays a central role in the pathophysiology of cartilage damage and degradation in arthritis. In the present study, we examined the effect of IL-1β on the expression of IL-1β, IL-6, IL-8, IL-11, tumor necrosis factor-α (TNF-α), and their receptors in human chondrocytes. The cells were cultured either with or without 100 U/ml of IL-1β for up to 28 days. The level of expression of the cytokines and their receptors was estimated by determining mRNA levels using real-time PCR or by determining protein levels using ELISA. The expression of IL-1β, IL-8, and TNF-α markedly increased in the presence of IL-1β after day 14 of culture. The expression of IL-6 and IL-11 increased greatly in the presence of IL-1β on day 1 and after day 14 of culture. The expression of IL-1β, IL-8, IL-11, and TNF-α receptors significantly decreased in the presence of IL-1β after day 14 of culture, whereas the expression of IL-6 receptor significantly increased. The expression of these cytokines, except for IL-6, decreased with the addition of human IL-1 receptor antagonist. These results suggest that IL-1β promotes the resolution system of cartilage matrix turnover through an increase in inflammatory cytokine production by chondrocytes and that it also may promote the autocrine action of IL-6 through an increase in IL-6 receptor expression in the cells.