Modulation of feeding by beta 2-microglobulin, a marker of immune activation

Increased levels of beta 2-microglobulin (part of the class I major histocompatibility complex molecules) in body fluids are associated with activation of the immune system and pathophysiological processes. Various anorexigenic cytokines, including interferon-gamma and tumor necrosis factor-alpha, induce the expression of class I molecules. Therefore, it is possible that beta 2-microglobulin may participate in the feeding suppression induced by cytokines or may have direct effects on feeding. In the present study, the effects of beta 2-microglobulin on the central regulation of feeding were investigated. Intracerebroventricular (ICV) microinfusion of beta 2-microglobulin (0.01-5.0 micrograms/rat) suppressed the nighttime food intake dose dependently. The most effective dose of beta 2-microglobulin, 5.0 micrograms/rat, decreased nighttime feeding by 38% and total daily food intake by 28%. Computerized analysis 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 the ICV microinfusion of 5.0 micrograms beta 2-microglobulin/rat; meal duration was not significantly affected in any interval. For the complete nighttime period, only meal size was significantly decreased. Cerebrospinal fluid-brain and rectal temperatures did not change significantly. ICV microinfusion of heat-treated beta 2-microglobulin or intraperitoneal administration of beta 2-microglobulin, in doses equivalent to those administered centrally, had no effect on food intake. The results suggest that beta 2-microglobulin may act centrally to decrease feeding, and this effect may participate in the anorexia frequently accompanying pathological processes.