CHEMOKINE-INDUCED FEVER - INTRACEREBROVENTRICULAR ACTIONS OF MIP-1 AND MIP-1-ALPHA IN RATS

THE central pyrogenic actions in the rat of doublet macrophage inflamm atory protein-1 (MIP-1) and MIP-1 alpha were determined by their intra cerebroventricular infusion. Doses of 560 pg and 11.2 ng of MIP-1 or 1 0.0 ng MIP-1 alpha infused into the third cerebral ventricle induced a long lasting fever. However, MIP-1 alpha was much less potent than MI P-1 in terms of intensity and longer latency. Overall, these cytokines are pyrogenic when acting on the walls of the third ventricle; howeve r, a dose 10 times greater than that injected directly into the anteri or hypothalamus is required to evoke fever, as based on earlier experi ments. Finally, circulating MIP-1 could act centrally by its entry thr ough the choroid plexus into the ventricular system of the brain.