INTERLEUKIN-1 RECEPTOR ON FIBROBLASTS FROM SYSTEMIC-SCLEROSIS PATIENTS INDUCES EXCESSIVE FUNCTIONAL-RESPONSES TO INTERLEUKIN-1-BETA

To determine if SSc fibroblasts are more sensitive to exogenous IL-1 than are normal fibroblasts, we studied the inductions of IL-6, prostaglandin E2 (PGE2), IL-1β mRNA production by IL-1-stimulated SSc and normal fibroblasts. The minimal IL-1β concentrations for stimulation of IL-6 and PGE2 production by SSc fibroblasts were 10-fold and 100-fold lower, respectively, than those for normal fibroblasts. The minimal IL-1β concentration for stimulation of IL-1β mRNA expression by SSc fibroblasts was also 10-fold lower than that for normal fibroblasts. These results suggest that the IL-1 signal transduction through IL-1R could be induced excessively in SSc fibroblasts. It is suggested that the IL-1 signal transduction plays an important role in the abnormal cytokine networks observed in the fibrosis of SSc. © 1993 Academic Press, Inc.