Naloxone differentially alters fevers induced by cytokines.
Interferon-alpha (IFN-alpha), a cytokine acting as an endogenous pyrogen and a putative activator of the opioid system, binds to opiate receptors in vitro. The mu opioid receptor antagonist, naloxone hydrochloride (NLX), attenuates IFN-alpha-induced increases in the firing rate of cold-sensitive neurons within thermosensitive areas of the brain. The influence of NLX on fevers induced by central endogenous pyrogens was investigated in rats. Subcutaneous (SQ) injection of NLX (1 mg/kg) was made 30 min prior to intracerebroventricular (ICV) injection of IFN-alpha 2b (7900IU). Alternatively, NLX (10 or 80 micrograms) was microinjected ICV 30 min prior to administration of IFN-alpha 2b. Administered SQ, NLX attenuated the febrile response to IFN-alpha 2b. In contrast, central (ICV) NLX did not attenuate fevers induced by IFN-alpha 2b. Animals previously exposed to both IFN-alpha 2b and NLX (SQ or ICV) subsequently lost their sensitivity to this cytokine, and also showed diminished reactivity to human recombinant interleukin-1 beta (hrIL-1 beta; 10 ng) and prostaglandin E2 (PGE2; 250 ng). These results suggest that systemic and central elements of the opioid system may play differential roles in temperature regulation. Previous administration of NLX and IFN-alpha 2b may alter the sensitivity of the CNS to subsequent injections of different pyrogens.
Zawada
W M
WM
Department of Medicine, University of Colorado School of Medicine, Denver 80262, USA.
Clarke
J
J
Ruwe
W D
WD
D000818:Animals; D015232:Dinoprostone / Q000008:administration & dosage / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced / Q000378:metabolism*; D006801:Humans; D007276:Injections, Intraventricular; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D016898:Interferon-alpha; D007375:Interleukin-1; D009292:Narcotic Antagonists; D011994:Recombinant Proteins; D009270:Naloxone; D015232:Dinoprostone