Substance P and calcitonin gene-related peptide increase IL-1β, IL-6 and TNFα secretion from human peripheral blood mononuclear cells

We found that substance P (SP) and calcitonin gene-related peptide (CGRP) (0.3-1 muM) increased, in a concentration-dependent manner, the basal secretion of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFalpha) from cultured lymphocyte-enriched mononuclear cells isolated from human peripheral blood. SP and CGRP (0.1 muM) synergistically increased basal TNFalpha secretion. Dynorphin A((1-17)) (0.1-1 muM) did not modify basal cytokine secretion. Lipopolysacharide (10 ng/ml)-induced cytokine secretion and [H-3]thymidine uptake were not altered by any neuropeptide (at 0.1 muM) Thus, SP and CGRP stimulate the production of pro-inflammatory cytokines from lymphocytes only at high concentrations, similar to those reached during tissue damage. (C) 2002 Published by Elsevier Science Ltd.