Calcitonin Gene-Related Peptide Enhances Cytokine-Induced IL-6 Production by Fibroblasts

The effect of calcitonin gone-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 enhanced that induced by IL-1β or TNFα at concentrations of 10-8M or higher. The action of CGRP was mediated by a CGRP-specific receptor. In contrast, calcitonin had no effect at all. A kinetic study of IL-6 activity in the culture supernatant showed that CGRP not only accelerated but also increased IL-6 production. Enhancement by CGRP of cytokine-dependent IL-6 production was ascribed to the increased accumulation of IL-6 mRNA. IL-1β-induced IL-6 production was maintained by CGRP after removal of IL-1β. The addition of CGRP to the culture following stimulation with IL-1β or IL-1β plus CGRP decelerated the decay of IL-6 mRNA. These results indicate that the augmenting effect of CGRP is mediated, at least in part, by the stabilization of IL-6-specific mRNA.