title: Presence of a reduced opioid response in interleukin-6 knock out mice.
abstract: Cytokines are known to influence neuronal functions. The purpose of this study was to investigate the putative role of the cytokine interleukin-6 (IL-6) in the pathways involved in opioid-mediated responses, by using IL-6-deficient mice. We reported that with a thermal stimulus IL-6-knock-out (IL-6KO) mice presented nociceptive thresholds similar to those measured in their controls. However, they showed a reduced analgesic response both to the restraint stress and to the administration of low doses of morphine. Hypothalamic levels of the opioid peptide beta-endorphin were significantly higher in IL-6KO mice than they were in their controls. The development of tolerance to the analgesic effect of morphine was more rapid in IL-6-deficient mice than in wild-type controls. Binding experiments showed that the number of opioid receptors in the midbrain, but not in the hypothalamus, decreased in IL-6KO mice. Autoradiographic binding analysis revealed that the density of mu receptors diminished while the delta-opioid receptors did not. These results suggest that IL-6 is necessary for a correct development of neuronal mechanisms involved in the response to both endogenous and exogenous opiates.
authors.affiliation: Department of Pharmacology, University of Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bianchi
authors.forename: R
authors.initials: R
authors.lastname: Maggi
authors.forename: F
authors.initials: F
authors.lastname: Pimpinelli
authors.forename: T
authors.initials: T
authors.lastname: Rubino
authors.forename: D
authors.initials: D
authors.lastname: Parolaro
authors.forename: V
authors.initials: V
authors.lastname: Poli
authors.forename: G
authors.initials: G
authors.lastname: Ciliberto
authors.forename: A E
authors.initials: AE
authors.lastname: Panerai
authors.forename: P
authors.initials: P
authors.lastname: Sacerdote
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D004361:Drug Tolerance; D007031:Hypothalamus / Q000737:chemistry / Q000502:physiology; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D009293:Opioid-Related Disorders / Q000378:metabolism / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000502:physiology; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000503:physiopathology; D001615:beta-Endorphin / Q000502:physiology*
chemical_list: D000701:Analgesics, Opioid; D015850:Interleukin-6; D017450:Receptors, Opioid, mu; D001615:beta-Endorphin; D009020:Morphine