The Antiinflammatory Actions of Melanocortins in the Central Nervous System Could be Mediated by MC3-R and NO May Participate in This Effect

CRAGNOLINI, ANDREA BEATRIZ; PERELLO, MARIO; SCHIÖTH, HELGI BIRGIR; SCIMONELLI, TERESA NIEVES

Los Cocos, Cordoba, Argentina

Congreso; XVII Reunión de la Sociedad Argentina de Neuroquímica; 2002

IL-1b is a potent activator of the hypothalamic–pituitary–adrenal (HPA) axis in rodents and IL-1b and glucocorticoid hormones represent two key mediators involved in the modulation of the neuroimmunoendocrine response to inflammation. Alpha-melanocyte-stimulating hormone (a-MSH), a neuroimmunomodulatory peptide is known to be involved in the control of host responses. In inflammatory cells, in the periphery and within the central nervous system, a-MSH modulates the production and action of proinflammatory cytokines. This broad influence occurs via endogenous melanocortin receptors. However, little information is currently available about the specific melanocortin receptors that mediate the modulatory effects that melanocortins exert on IL-1 effects on the central nervous system. In this study, we carried out a series of studies to determine the melanocortin receptors that are involved in the inhibition by melanocortins of the HPA-axis activation induced by IL-1b. In addition the possibility has been investigated that the effect of MSH may be mediated via NO. The i.c.v. injection of different doses of IL-1b (1, 12.5, or 25 ng/μL) produced significant changes in corticosterone plasma levels, compared to vehicle-treated animal. Administration of a-MSH (1 ug) did not inhibit the effect of the cytokine. However, g-MSH (1 μg), an MC3-R agonist, resulted in a significant reduction on plasma  corticosterone levels. Neither peptide modified corticosterone release when administered as a single injection. The treatment with IL-1b induced an increase in NO production in hypothalamus and this effect was inhibited by the melanocortins. The results of the present study suggest that the principal receptor involved in the antiinflammatory actions of melanocortins in the central nervous system is MC3-R, and that NO may be mediating melanocortin effects.