Hypothalamic interaction between macrophage inflammatory protein-1 alpha (MIP-1 alpha) and MIP-1 beta in rats: a new level for fever control?

1. The microinjection of macrophage inflammatory protein-1 (MIP-1 alpha; 5.0 and 25 pg) into the anterior hypothalamic, preoptic area (AHPOA) induced a slow onset; monophasic fever in rats that persisted for a long period. Microinjection of 25 pg MIP-1 beta into the AHPOA induced a fever of rapid onset, whereas 5.0 pg MIP-1 beta did not alter body temperature (Tb) significantly. When either MIP-1 alpha or MIP-1 beta was heated to 70 degrees C for 30 min prior to their injection, no pyrexic response was produced. 2. The concurrent microinjection of 25 pg MIP-1 alpha and 25 pg MIP-1 beta into the AHPOA attenuated the effects on Tb of either cytokine alone. However, pretreatment with either 5.0 pg MIP-1 beta or 5.0 pg MIP-1 alpha suppressed the febrile response induced by 25 pg MIP-1 alpha or 25 pg MIP-1 beta, given at the same site, respectively. 3. The present experiments show that MIP-1 alpha and MIP-1 beta are active individually and possess distinct differences in their evocation of a febrile response. Further, our results suggest a functional antagonism between MIP-1 alpha and MIP-1 beta that could represent a new level in the development of fever.