Hypothalamic indomethacin fails to block fever induced in rats by central macrophage inflammatory protein-1 (MIP-1).
This investigation examined the extent to which the activity of a prostaglandin (PG) in the anterior hypothalamic, preoptic area (AH/POA) of the rat plays a role in the intense fever induced by macrophage inflammatory protein-1 (MIP-1) applied directly to this anatomical region. For the microinjection of both a PG synthesis inhibitor, indomethacin, and MIP-1 into sites within the AH/POA, guide cannulae were implanted chronically just above this pyrogen-reactive region. Postoperatively, the body temperature (Tb) of each rat was monitored in the unrestrained condition by means of a colonic thermistor probe. MIP-1 microinjected into the AH/POA in a 0.5-microliter volume evoked a biphasic fever when given in a dose of 5.6 picograms (pg) and a monophasic fever in a dose of 28 pg. The latency of the febrile response was ordinarily 15 min with an asymptote of 1.5 degrees C reached ordinarily within 2.0-2.5 h. When the cytokine-reactive site in the AH/POA was pretreated with indomethacin microinjected in an efficacious dose of 0.5 microgram, the MIP-1 fever evoked by 5.6 pg was not inhibited. Further, pretreatment of AH/POA sites with indomethacin prior to the higher 28-pg dose of MIP-1 delayed the febrile response but did not block it. As a systemic control, indomethacin also was administered intraperitoneally in a dose of 5.0 mg/kg, again 15 min prior to the microinjection of MIP-1 into the AH/POA. In this case, indomethacin only partially attenuated but did not block the fever evoked by either dose of MIP-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Miñano
F J
FJ
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858.
Vizcaino
M
M
Myers
R D
RD
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects; D054407:Chemokine CCL4; D016207:Cytokines / Q000037:antagonists & inhibitors*; D004591:Electrophoresis, Polyacrylamide Gel; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control*; D007031:Hypothalamus / Q000187:drug effects*; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D007267:Injections; D007274:Injections, Intraperitoneal; D019402:Macrophage Inflammatory Proteins; D008297:Male; D008845:Microinjections; D015846:Monokines / Q000037:antagonists & inhibitors*; D011301:Preoptic Area; D051381:Rats; D011919:Rats, Inbred Strains
D054407:Chemokine CCL4; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D007213:Indomethacin