SUPPRESSION OF THE FUNCTIONAL-ACTIVITY OF IL-2-ACTIVATED LYMPHOCYTES BY CGRP

CGRP is a 37-amino acid neuropeptide found in the central and peripher al nervous systems as well as the nerve endings in lymphoid organs. Sp ecific CGRP receptors are present on both T and B lymphocytes. There i s increasing evidence that CGRP plays a role in regulation of the immu ne response. However, few investigations have examined the effects of CGRP on lymphocyte effector functions. In this report, CGRP (0.1 nM-1 mu M) was shown to cause concentration-dependent inhibition of IL-2-ac tivated lymphocyte growth inhibition of the fungus Candida albicans an d cytotoxic activity for tumor cells. Maximum inhibition of lymphocyte activity by CGRP was 47.4% for the hyphae of C. albicans, 44.8% for a natural killer cell susceptible cell line, and 52.9% for a natural ki ller cell-resistant cell line. CGRP-mediated inhibition of lymphocyte function was mimicked by 8-bromo-cAMP (1 mM) and was correlated in a c oncentration-dependent manner with an increase in intracellular levels of cAMP. These increases were potentiated by pretreatment of the lymp hocytes with 3-isobutyl-1-methylxanthine (0.5 mM, 10 min), an inhibito r of the cAMP phosphodiesterase. hCGRP(8-37), a selective blocker of t he CGRP(1) receptor, abrogated the effect of CGRP on lymphocyte functi on and on intracellular cAMP level elevation induced by rCGRP. CGRP ha d no direct effect on the capacity of IL-2-activated lymphocytes to ad here to the hyphae of C. albicans. However, both CGRP and 8-bromo-cAMP diminished the capacity of the lymphocytes to release cytoplasmic gra nular content when stimulated by the hyphae of C. albicans. These data show that CGRP inhibits functional activity of IL-2-activated lymphoc ytes and suggest that hCGRP(8-37) may be a useful tool for assessing t he role of CGRP in the immune system. (C) 1995 Academic Press, Inc.