Peripheral metabolic effects of cytokines in the central nervous system

HIV-1 actively infects microglia in the CNS and stimulates these cells to synthesize proinflammatory cytokines The purpose of this study was to investigate the capacity for central cytokines (i.e., in the CNS) to induce symptoms indicative of AIDS cachexia. A cannula was stereotaxically placed in the lateral cerebral ventricle of adult male Wistar-Firth rats (270-300 g) for intracerebroventricular (ICV) injection of recombinant human TNFa and ILip. After one week, rats were weighed, subjected to a 5-min social exploration test to assess motivation, and injected ICV with vehicle (5 ul) or one of three doses of TNFa (25, 50 or 100 ng) or IL-1 (12.5, 25 or 50 ng) Body temperature was measured telemetrically at 30 min intervals and at 4 h, rats were subjected to the social exploration test and sacrificed for tissue sample collection Food was withheld throughout Central injection of either IL-1 or TNFa depressed social behavior, induced fever, and increased plasma corticosterone (P<01). Centra! IL-1 P and TNFa also induced substantial weight loss (P<01) and increased plasma IL-6 concentration (P<01). Although IL-6 has been reported to induce hypertriglyceridemia and was elevated by ICV IL-1 p and TNFa, neither cytokine increased serum triglycérides or NEF As (P> 05). These data suggest cytokines in the'CNS are important for mediating systemic acute-phase responses, but their involvement, if any, in hypertriglyceridemia is not clear.