Action of cyclosporine on fever induced in rats by intrahypothalamic injection of macrophage inflammatory protein-1 (MIP-1).

In order to examine the central mechanism of pyrexic action of macrophage inflammatory protein-1 (MIP-1), guide cannulae for injections were implanted stereotaxically just above the anterior hypothalamic, pre-optic area of the rat. Following post-operative recovery, the body temperature (Tb) of each rat was monitored by a colonic thermistor probe over a test interval of 4 hr. Injected in a 0.5 microliter volume into the anterior hypothalamic pre-optic area, MIP-1, in a dose of 5.6 or 28 pg, evoked an intense fever with a latency of 15-30 min. Pretreatment of the anterior hypothalamic pre-optic area with 1.0 microgram cyclosporine A (CsA), delivered in a volume of 0.5 microliter, delayed the onset of the fever induced by 5.6 pg MIP-1, injected at the same site. Similar injections of CsA also attenuated significantly the magnitude of the fever, following either the 5.6 or 28 pg dose of MIP-1. As a systemic control, 15 mg/kg CsA was administered intraperitoneally, 2.0 hr before the injection of MIP-1 in the anterior hypothalamic pre-optic area. By this route, CsA also delayed the rise in temperature but the fever induced by 5.6 pg MIP-1 reached the same magnitude as that after MIP-1 alone. Conversely, intraperitoneal administration of CsA did not antagonize the pyrexic response evoked by 28 pg MIP-1, injected into the anterior hypothalamic pre-optic area, but rather enhanced the fever.(ABSTRACT TRUNCATED AT 250 WORDS)