Effect of a mu-opioid receptor-selective antagonist on interleukin-6 fever.
The endogenous opioid system has been found to be involved in fever caused by pyrogens. Recent work in our laboratory has demonstrated that the mu-opioid receptor is involved in interleukin-1beta (IL-1beta)- and in lipopolysaccharide (LPS)-induced fevers. In the present study, we have investigated the role of the mu-opioid receptor in the preoptic anterior hypothalamus (POAH) in fever induced by interleukin-6 (IL-6). Following stereotaxic implantation of a guide cannula into the POAH for microinjection, radio transmitters to monitor body temperature (Tb) continuously were inserted intraperitoneally. Adult male Sprague-Dawley rats were microinjected with 0.5 microg of the selective mu-opioid receptor antagonist, cyclic D-phe-Cys-Try-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP), into the POAH. Thirty min later, IL-6 (100 ng) was injected into the POAH. CTAP significantly blocked the IL-6 fever. CTAP alone had no effect on Tb during the 390-min recording period. These data indicate that mu-opioid receptors within the POAH mediate IL-6 fever and add to the increasing evidence that the opioid system is involved in the pathogenesis of fever in rats.
Benamar
Khalid
K
Center for Substance Abuse Research and Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA. kbenamar@hotmail.com
Geller
Ellen B
EB
Adler
Martin W
MW
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control*; D007032:Hypothalamus, Anterior / Q000187:drug effects* / Q000378:metabolism; D015850:Interleukin-6 / Q000009:adverse effects*; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010446:Peptide Fragments; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013004:Somatostatin
C529311:CTAP octapeptide; D015850:Interleukin-6; D009292:Narcotic Antagonists; D010446:Peptide Fragments; D010455:Peptides; D017450:Receptors, Opioid, mu; D013004:Somatostatin