Calcitonin gene-related peptide indirectly inhibits IL-7 responses in pre-B cells by induction of IL-6 and TNF-? in bone marrow

Abstract

Calcitonin gene-related peptide (CGRP) has inflammatory and immunoregulatory properties. CGRP directly inhibits IL-7 induced proliferation in developing B cells and also induces soluble factors that inhibit IL-7 responses. We identified 2 cytokines, IL-6 and TNF-?, induced by CGRP, that inhibit IL-7 pre-B cell responses. CGRP induction of IL-6 and TNF-? mRNA in long-term bone marrow cultures is transient and IL-6 or TNF-? inhibit IL-7 induced colony formation by 60%. When added with CGRP, colony formation is completely inhibited. TNF-? directly inhibits IL-7 responses in B220+/IgM? cells whereas IL-6 inhibits only colony formation with whole bone marrow. This suggests that the effect of IL-6 is mediated by other cells in the bone marrow. These results suggest that the indirect effect of CGRP on IL-7 depends in part on induction of IL-6 and TNF-?.