CALCITONIN-GENE-RELATED PEPTIDE ENHANCES CYTOKINE-INDUCED IL-6 PRODUCTION BY FIBROBLASTS

The effect of calcitonin gene-related peptide (CGRP) was investigated on cytokine-induced IL-6 production by Swiss 3T3 fibroblasts. CGRP by itself had little effect on IL-6 production, and substantially enhance d that induced by IL-1 beta or TNF alpha at concentrations of 10(-8) M or higher. The action of CGRP was mediated by a CGRP-specific recepto r. In contrast, calcitonin had no effect at all. A kinetic study of IL -6 activity in the culture supernatant showed that CGRP not only accel erated but also increased IL-6 production. Enhancement by CGRP of cyto kine-dependent IL-6 production was ascribed to the increased accumulat ion of IL-6 mRNA. IL-1 beta-induced IL-6 production was maintained by CGRP after removal of IL-1 beta. The addition of CGRP to the culture f ollowing stimulation with IL-1 beta or IL-1 beta plus CGRP decelerated the decay of IL-6 mRNA. These results indicate that the augmenting ef fect of CGRP is mediated, at least in part, by the stabilization Of IL -6-specific mRNA. (C) 1995 Academic Press, Inc.