MODULATION OF FEEDING BY BETA(2)-MICROGLOBULIN, A MARKER OF IMMUNE ACTIVATION

Increased levels of beta(2)-microglobulin (part of the class I major h istocompatibility complex molecules) in body fluids are associated wit h activation of the immune system and pathophysiological processes. Va rious anorexigenic cytokines, including interferon-gamma and tumor nec rosis factor-alpha, induce the expression of class I molecules. Theref ore, it is possible that beta(2)- microglobulin may participate in the feeding suppression induced by cytokines or may have direct effects o n feeding. In the present study, the effects of beta(2)-microglobulin on the central regulation of feeding were investigated. Intracerebrove ntricular (ICV) microinfusion of beta(2)-microglobulin (0.01-5.0 mu g/ rat) suppressed the nighttime food intake dose dependently. The most e ffective dose of beta(2)-microglobulin, 5.0 mu g/rat, decreased nightt ime feeding by 38% and total daily food intake by 28%. Computerized an alysis of behavioral patterns demonstrated that beta(2)-microglobulin decreased meal size and meal frequency during the initial 4-h interval , but decreased only meal size during the second 4-h interval after th e ICV microinfusion of 5.0 mu g beta(2)-microglobulin/rat; meal durati on was not significantly affected in any interval. For the complete ni ghttime period, only meal size was significantly decreased. Cerebrospi nal fluid-brain and rectal temperatures did not change significantly. ICV microinfusion of heat-treated beta(2)-microglobulin or intraperito neal administration of beta(2)-microglobulin, in doses equivalent to t hose administered centrally, had no effect on food intake. The results suggest that beta(2)-microglobulin may act centrally to decrease feed ing, and this effect may participate in the anorexia frequently accomp anying pathological processes.