Modulating effects of sensory and autonomic neuropeptides on murine splenocyte proliferation and cytokine secretion induced by Leishmania major

The intimate, bidirectional link between neuroendocrine and immune systems is now accepted. A modulating effect of the nervous system on immune and in flammatory responses has been corroborated by identification of neuropeptid e receptors on immunocompetent cells and the finding that neuropeptides can regulate leukocyte functions. The present study was undertaken to investig ate the possible immunomodulatory role of sensory (SOM, CGRP and SP) and au tonomic (VIP and NPY) neuropeptides in a murine model of cutaneous]leishman iasis, using two genetically different inbred mouse strains, BALB/c and C57 BL/6, respectively susceptible and resistant to Leishmania (L.) major infec tion. The parameters studied were extent of splenocyte proliferation, as me asured by thymidine uptake, and the ability of these cells to secrete IFN-g amma and IL-4 by using a two-site ELISA, upon in vitro challenge with L. ma jor parasites and addition of the neuropeptides. The resistant mouse spleno cyte proliferation was enhanced by SOM, CGRP, and VIP at 10(-5), 10(-6) and 10(-9) M concentration, respectively, but was inhibited by NPY at 10(-5) M . Proliferation of the splenocytes from the susceptible strain was inhibite d by SOM (10(-11) M) and CGRP(10(-5) M). Somatostatin, at various concentra tions, stimulated IFN-gamma secretion in both mouse strain splenocytes, and IL-4 production in the susceptible mouse. Calcitonin gene-related peptide enhanced IFN-gamma secretion in susceptible mouse splenocytes at 10(-6), 10 (-7) and 10(-9) M, as did VIP at 10(-10) M and NPY at 10(-7) M.