Fever and feeding: Differential actions of macrophage inflammatory protein-1 (MIP-1), MIP-1? and MIP-1? on rat hypothalamus

Abstract

Changes in body temperature (Tb) and feeding were characterized in unrestrained rats following the micro-injection into the anterior hypothalamic preoptic area (AH/POA) of macrophage inflammatory protein-1 (MIP-1), MIP-1 alpha or MIP-1 beta. After the rats recovered from the stereotaxic implantation of a single guide tube placed in the AH/POA, either one of the MIP-1 compounds or control CSF was micro-injected in a volume of 1.0 microliter into this area. Changes in body temperature (Tb) and food and water intakes were monitored throughout each experiment. When micro-injected into the AH/POA in a dose of 28 or 280 pg, doublet MIP-1 and MIP-1 beta evoked a monophasic fever which increased above baseline to a mean maximum of 2.17 +/- 0.14 degrees C and 2.1 +/- 0.24 degrees C, respectively. MIP-1 alpha micro-injected similarly evoked a biphasic fever, with the Tb declining transiently at the 30 min point > or = 0.4 degrees C lower than the congruent rises in Tb evoked by doublet MIP-1 or MIP-1 beta. The secondary rise in Tb induced by MIP-1 alpha had a latency of 1.5-2.0 hrs and reached a maximum of 1.56 +/- 0.16 degrees C. Although all three cytokines significantly attenuated the rats' mean intake of food during the 24 hr interval after their micro-injection into the AH/POA, doublet MIP-1 exerted the most potent anorexic effect in comparison to that of the saline control rats. However, neither body weight nor intake of water was altered significantly by the three cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)