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 alph a; 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 (T-b) significantly. When either MIP-1 alpha or MIP-1 beta was heated to 70 degrees C for 30 min prior to their injection, no py rexic response was produced. 2. The concurrent microinjection of 25 pg MIP-1 alpha and 25 pg MIP-1 beta into the AHPOA attenuated the effect s on T-b 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 s ite, respectively. 3. The present experiments show that MIP-1 alpha, a nd MIP-1 beta are active individually and possess distinct differences in their evocation of a febrile response. Further, our results sugges t a functional antagonism between MIP-1 alpha and MIP-1 beta that coul d represent a new level in the development of fever.