title: Neuromodulation of fever: apparent involvement of opioids.
abstract: It was recently reported that the opiate antagonist, naloxone (Nal), blocks the changes induced by the endogenous pyrogen, interferon-alpha 2 (IFN), in the electrical activity of hypothalamic thermosensitive neurons in rat brain slice preparations. This study was undertaken to determine whether the pyrogenic response to this cytokine might, therefore, be modulated through Nal-reversible opiate receptors. To examine this possibility, conscious guinea pigs were injected IV with recombinant human (rh) IFN (10 MU/animal), or, for comparison, with S. enteritidis endotoxin (lipopolysaccharide, LPS; 2 micrograms/kg), rh tumor necrosis factor-alpha (TNF; 20 micrograms/kg), or rh interleukin-6 (IL6; 50 micrograms/kg); Nal (10 mg/kg, SC) was administered immediately before the pyrogens. And also for comparison, in separate experiments, indomethacin (Indo; 10 mg/kg, IM) was injected 20 min before the pyrogens. Both Nal and Indo abolished the febrile rises evoked by IFN, TNF, and IL6. Nal reduced the first and suppressed the second of the characteristically bimodal febrile response to LPS; Indo depressed both peaks. Neither blocker had any significant thermal effect by itself. These results suggest that two processes may mediate the pyrogenic effects of these substances, viz., an endogenous opioid- and a PGE-dependent mechanism.
authors.affiliation: Department of Physiology and Biophysics, University of Tennessee, Memphis 38163.
authors.forename: C M
authors.initials: CM
authors.lastname: Blatteis
authors.forename: L
authors.initials: L
authors.lastname: Xin
authors.forename: N
authors.initials: N
authors.lastname: Quan
mesh_terms: D000818:Animals; D005334:Fever / Q000139:chemically induced / Q000378:metabolism*; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009270:Naloxone; D007213:Indomethacin