Calcitonin-gene related peptide (CGRP) inhibits interleukin-7-induced pre-B cell colony formation

Calcitonin gene-related peptide (CGRP) is a sensory neuropeptide with inflammatory and immunoregulatory activities. Its role in B lymphocyte development was investigated using a pre-B cell colony-forming assay. Physiological concentrations of CGRP inhibited pre-B cell responses to interleukin-7 (IL-7). Inhibition was specific in that it was blocked by the CGRP antagonist CGRP8-37. Adrenomedulin, substance P, and calcitonin had no effect on B cell precursor responses. Similar responses were observed with B220+/IgM- B cell precursors. Inhibition of IL-7 responses in B220+/IgM- cells suggests that CGRP has a direct effect on B cell precursors. Studies with cultured bone marrow-adherent cells found that CGRP also has an indirect effect on IL-7 responses. Cultured bone marrow-adherent cells were treated with CGRP for 24 h, and anti-CGRP was added to the supernatants to neutralize CGRP. Concentrations of CGRP as low as 0.01 nM induced a factor that inhibited colony formation. In contrast, CGRP did not induce an inhibitory factor in cultured bone marrow macrophages, suggesting that CGRP induces an inhibitory factor in some adherent cell other than macrophages. The results show that CGRP has both direct and indirect effects on developing B cells and support a role for CGRP as an inhibitor of early B cell development.