Involvement of the cocaine-amphetamine regulated transcript peptide (CART 55-102) in the modulation of rat immune cell activity.

OBJECTIVE: Cocaine-amphetamine regulated transcript peptides (CART) belong to a neuropeptide family expressed in the central nervous system, especially in the hypothalamus, and also in peripheral tissues. The physiological functions of CART include modulation of pituitary hormone release, regulation of body weight, and the control of feeding behavior and metabolic activity. The reciprocal relationships between CART and immune system function have to be established. Therefore, in the present study we aimed to investigate the influence of CART, administered intracerebroventricularly (icv), on selected immune parameters and pituitary-adrenal axis hormone secretion in the rat.

RESEARCH METHODS: In rats submitted to icv infusion of CART or artificial cerebrospinal fluid (aCSF, control) selected immune parameters: splenocyte proliferation (spontaneous and mitogen-stimulated) and peritoneal leukocyte (PTL) activity (spontaneous and phorbol myristate acetate (PMA)-stimulated) were examined 60 and 120 min after treatment. The direct effect of CART on splenocytes in culture in vitro was also examined. Concentration of adrenocorticotrophic hormone (ACTH) and corticosterone was also measured in serum of control and CART infused rats.

RESULTS: Splenocytes isolated 60 min after CART infusion exhibited a decreased, albeit non-significant, ability to proliferate spontaneously and were unable to answering to the mitogenic stimulation. This effect was not seen 120 min after CART treatment, which restored splenocyte proliferation decreased by aCSF infusion. CART addition in vitro did not influence proliferation of splenocytes from control rats. Spontaneous activity of peritoneal leukocytes was not modified by CART infusion. PMA-stimulated PTL activity was significantly decreased in aCSF-infused rats 120 min after treatment and CART infusion antagonized this effect. Non-significant increase in serum cortisol after 60 min followed by a significant decrease after 120 min with no change in ACTH concentration was found.

CONCLUSION: The immunomodulatory activity of icv-infused CART appears to consist in the creation of a short-lasting immunosuppressive internal milieu, followed by the immunostimulatory one. This first effect was most probably due to the activation of the HPA axis and/or other immunosuppressive peptides, but not through the direct action of CART on immune cells. Thus, CART appears to be short-lasting and indirect modulator of immunity.