The role of brain cytokines in mediating the behavioral and neuroendocrine effects of intracerebral Mycoplasma fermentans (original) (raw)

Intracerebral administration of Mycoplasma fermentans MF , a small microorganism that has been found in the brain of some AIDS Ž . patients, induces behavioral and neuroendocrine alterations in rats. To examine the role of tumor necrosis factor-a TNFa and Ž . interleukin-1 IL-1 in mediating these effects we measured MF-induced expression of TNFa and IL-1b mRNA in various brain regions, Ž . and the effects of TNFa synthesis blockers and IL-1 receptor antagonist IL-1ra on MF-induced sickness behavior and adrenocortical Ž . activation. Intracerebroventricular i.c.v. administration of heat-inactivated MF induced the expression of both TNFa and IL-1b mRNA in the cortex, dorsal hippocampus, amygdala, and hypothalamus. Pre-treatment of rats with either TNFa synthesis blockers, pentoxifylline or rolipram, or with IL-1ra did not attenuate MF-induced anorexia, body weight loss, and suppression of social behavior. However, simultaneous administration of both pentoxifylline and IL-1ra markedly attenuated MF-induced anorexia and body weight loss, but had no effect on the suppression of social behavior. Pre-treatment with pentoxifylline, but not with IL-1ra, significantly attenuated MF-induced Ž . corticosterone CS secretion. Together, these findings indicate that both TNFa and IL-1 participate, in a complementary manner, in mediating some of the behavioral effects of MF, whereas only TNFa , but not IL-1, is involved in mediating MF-induced adrenocortical activation. We suggest that cytokines within the brain are involved in mediating at least some of the neurobehavioral and neuroendocrine abnormalities that may be produced by MF in AIDS patients. q periphery and in the brain, and affect neurobehavioral functions via specific receptors found in various brain w x structures 60 . Direct administration of TNFa or IL-1b, either peripherally or into the cerebral ventricle, produces marked behavioral and neuroendocrine effects, including a suppression of appetite, motor activity, exploratory, social, and sexual behavior, increased slow wave sleep, general malaise, altered pain sensitivity, and enhanced secretion of Ž . corticotropin-releasing hormone CRH , ACTH and glucow x corticoids 6,17,32,41,67 . Moreover, antibodies against particular cytokines, or cytokine antagonists attenuate or block the behavioral effects of immune challenges w x 4, and the activation of the HPA axis in w x various medical conditions 20,51,54,57 .