Interleukin-1 beta enhances the response of human articular chondrocytes to extracellular ATP

It has been observed that both interleukin-1 (IL-1) and extracellular ATP stimulate the production of prostaglandin E (PGE) by human articular chondrocytes in monolayer culture. The combined effects of recombinant human IL-1 beta and ATP were therefore studied using these cells. IL-1 beta rapidly enhanced the response to a maximally effective concentration of ATP (100 microM). On continuous exposure of the cells to the cytokine, its effect was greatest after approx. 24 h and tended to decline thereafter. The enhancement of the response to 100 microM ATP by IL-1 beta was dose-dependent. Removal of IL-1 beta prior to treating the cells with 100 microM ATP did not affect the degree of enhancement of the response. The effect of the cytokine on the response to suboptimal concentrations of extracellular ATP was also tested. IL-1 beta lowered the minimum concentration of ATP required to elicit an increase in the production of PGE by human articular chondrocytes. These findings are of interest, since they indicate a synergistic interaction between a cytokine and a purinergic agonist. Moreover, since both the sensitivity of the cells to extracellular ATP and the maximum response to this agent were enhanced, it is possible that IL-1 modulates more than one step in the process of P2-purinoceptor-mediated stimulation of PGE production. These observations may be relevant to the pathogenesis of some forms of arthritis.