title: Interleukin-1β and interleukin-6 enhance thermal prolongation of the LCR in decerebrate piglets.
abstract: Thermal stress and prior upper respiratory tract infection are risk factors for the Sudden Infant Death Syndrome. The adverse effects of prior infection are likely mediated by interleukin-1β (IL-1β). Therefore, we examined the single and combined effects of IL-1β and elevated body temperature on the duration of the Laryngeal Chemoreflex (LCR) in decerebrate neonatal piglets ranging in age from post-natal day (P) 3 to P7. We examined the effects of intraperitoneal (I.P.) injections of 0.3mg/Kg IL-1β with or without I.P. 10mg/Kg indomethacin pretreatment on the duration of the LCR, and in the same animals we also examined the duration of the LCR when body temperature was elevated approximately 2°C. We found that IL-1β significantly increased the duration of the LCR even when body temperature was held constant. There was a significant multiplicative effect when elevated body temperature was combined with IL-1β treatment: prolongation of the LCR was significantly greater than the sum of independent thermal and IL-1β-induced prolongations of the LCR. The effects of IL-1β, but not elevated body temperature, were blocked by pretreatment with indomethacin alone. We also tested the interaction between IL-6 given directly into the nucleus of the solitary tract (NTS) bilaterally in 100ngm microinjections of 50μL and pretreatment with indomethacin. Here again, there was a multiplicative effect of IL-6 treatment and elevated body temperature, which significantly prolonged the LCR. The effect of IL-6 on the LCR, but not elevated body temperature, was blocked by pretreatment with indomethacin. We conclude that cytokines interact with elevated body temperature, probably through direct thermal effects on TRPV1 receptors expressed pre-synaptically in the NTS and through cytokine-dependent sensitization of the TRPV1 receptor. This sensitization is likely initiated by cyclo-oxygenase-2 dependent synthesis of prostaglandin E2, which is stimulated by elevated levels of IL-1β or IL-6. Inflammatory sensitization of the LCR coupled with thermal prolongation of the LCR may increase the propensity for apnea and Sudden Infant Death Syndrome.
authors.affiliation: Department of Physiology & Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, United States.
authors.forename: Luxi
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Physiology & Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, United States.
authors.forename: Donald
authors.initials: D
authors.lastname: Bartlett
authors.affiliation: Department of Physiology & Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, United States. Electronic address: james.c.leiter@dartmouth.EDU.
authors.forename: J C
authors.initials: JC
authors.lastname: Leiter
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003655:Decerebrate State; D004195:Disease Models, Animal; D005260:Female; D005334:Fever / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D053583:Interleukin-1beta / Q000008:administration & dosage / Q000378:metabolism*; D015850:Interleukin-6 / Q000008:administration & dosage / Q000378:metabolism*; D007830:Larynx / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010791:Phrenic Nerve / Q000187:drug effects / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D012119:Respiration / Q000187:drug effects; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism*; D013552:Swine; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: D016861:Cyclooxygenase Inhibitors; D053583:Interleukin-1beta; D015850:Interleukin-6; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin
keywords: Hyperthermia; Interleukin-1β; Interleukin-6; Laryngeal chemoreflex; Nucleus of the solitary tract; SIDS