title: Modulating effects of sensory and autonomic neuropeptides on murine splenocyte proliferation and cytokine secretion induced by Leishmania major.
abstract: The intimate, bidirectional link between neuroendocrine and immune systems is now accepted. A modulating effect of the nervous system on immune and inflammatory responses has been corroborated by identification of neuropeptide receptors on immunocompetent cells and the finding that neuropeptides can regulate leukocyte functions. The present study was undertaken to investigate the possible immunomodulatory role of sensory (SOM, CGRP and SP) and autonomic (VIP and NPY) neuropeptides in a murine model of cutaneous leishmaniasis, using two genetically different inbred mouse strains, BALB/c and C57BL/6, respectively susceptible and resistant to Leishmania (L.) major infection. The parameters studied were extent of splenocyte proliferation, as measured by thymidine uptake, and the ability of these cells to secrete IFN-gamma and IL-4 by using a two-site ELISA, upon in vitro challenge with L. major parasites and addition of the neuropeptides. The resistant mouse splenocyte 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 inhibited by SOM (10(-11) M) and CGRP(10(-5) M). Somatostatin, at various concentrations, 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. Vasoactive intestinal peptide also stimulated IL-4 production in BALB/c splenocytes at all concentrations used. Substance P had no effect on either cell proliferation or cytokine secretion in either of the two mouse strains. These findings indicate that the nervous system, represented by sensory and autonomic nerve terminals and their content of neuromediators, may be involved in the pathophysiology of cutaneous leishmaniasis.
authors.affiliation: Department of Dermatology, Karolinska Hospital, Stockholm, Sweden.
authors.forename: A A
authors.initials: AA
authors.lastname: Ahmed
authors.forename: V
authors.initials: V
authors.lastname: Mutt
authors.forename: K
authors.initials: K
authors.lastname: Nordlind
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018320:Leishmania major / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009478:Neuropeptide Y / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology*; D013004:Somatostatin / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
chemical_list: D016207:Cytokines; D009478:Neuropeptide Y; D009479:Neuropeptides; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D015740:Calcitonin Gene-Related Peptide