The role of brain cytokines in mediating the behavioral and neuroendocrineeffects of intracerebral Mycoplasma fermentans

Intracerebral administration of Mycoplasma fermentans (MF), a small microor ganism that has been found in the brain of some AIDS patients, induces beha vioral and neuroendocrine alterations in rats. To examine the role of tumor necrosis factor-alpha (TNF alpha) and interleukin-1 (IL-1) in mediating th ese effects we measured MF-induced expression of TNF alpha and,IL-1 beta mR NA in various brain regions, and the effects of TNF alpha synthesis blocker s and IL-1 receptor antagonist (IL-1ra) on MF-induced sickness behavior and adrenocortical activation. Intracerebroventricular (i.c.v.) administration of heat-inactivated MF induced the expression of both TNF alpha and IL-1 b eta mRNA in the cortex, dorsal hippocampus, amygdala, and hypothalamus. Pre -treatment of rats with either TNF alpha synthesis blockers, pentoxifylline or rolipram, or with IL-1ra did not attenuate MF-induced anorexia, body we ight loss, and suppression of social behavior. However, simultaneous admini stration of both pentoxifylline and IL-1ra markedly attenuated MF-induced a norexia and body weight loss, but had no effect on the suppression of socia l behavior. Pre-treatment with pentoxifylline, but not with IL-1ra, signifi cantly attenuated MF-induced corticosterone (CS) secretion. Together, these findings indicate that both TNF alpha and IL-1 participate, in a complemen tary manner, in mediating some of the behavioral effects of MF, whereas onl y TNF alpha, but not IL-1, is involved in mediating MF-induced adrenocortic al activation. We suggest that cytokines within the brain are involved in m ediating at least some of the neurobehavioral and neuroendocrine abnormalit ies that may be produced by MF in AIDS patients. (C) 1999 Elsevier Science B.V. All rights reserved.