title: Cyclooxygenase pathway in modulation of the ventilatory response to hypercapnia by interleukin-1β in rats.
abstract: At the present time very little is known about interactions between the systemic inflammatory and ventilatory control. Our previous study has demonstrated that the elevation of the major inflammatory cytokines interleukin-1β (IL-1β) in the cerebrospinal fluid (CSF) may affect the control of ventilation. The aim of the current study was to compare the respiratory effects of IL-1β before and after pretreatment with diclofenac, a nonspecific cyclooxygenase (COX) inhibitor. Using the method of rebreathing with hyperoxic gas mixture we demonstrate that the slope of the ventilatory response to carbon dioxide decreased almost twofold from 5.6±0.52 to 2.5±0.28 ml min(-1)mmHg(-1) (p<0.01) 40 min after cerebroventricular administration of IL-1β. In contrast, the basal level of lung ventilation increased after the elevation of IL-1β in CSF. Diclofenac pretreatment eliminated these respiratory effects of IL-1β. The data indicate that the ability of IL-1β to enhance basal ventilation and to reduce the ventilatory hypercapnic response is mediated by the COX pathway.
authors.affiliation: Laboratory of Respiratory Physiology, Pavlov Institute of Physiology of RAS, nab. Makarova 6, 199034 St.-Petersburg, Russia. Electronic address: n_aleks@yahoo.com.
authors.forename: N P
authors.initials: NP
authors.lastname: Aleksandrova
authors.affiliation: Laboratory of Respiratory Physiology, Pavlov Institute of Physiology of RAS, nab. Makarova 6, 199034 St.-Petersburg, Russia.
authors.forename: G A
authors.initials: GA
authors.lastname: Danilova
authors.affiliation: Department of Anatomy and Physiology of Humans and Animals, Herzen State Pedagogical University of Russia, St.-Petersburg, Russia.
authors.forename: V G
authors.initials: VG
authors.lastname: Aleksandrov
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D002245:Carbon Dioxide / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology; D006935:Hypercapnia / Q000503:physiopathology*; D053583:Interleukin-1beta / Q000008:administration & dosage / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D012119:Respiration / Q000187:drug effects*; D013997:Time Factors
chemical_list: D016861:Cyclooxygenase Inhibitors; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D002245:Carbon Dioxide; D004008:Diclofenac; D011451:Prostaglandin-Endoperoxide Synthases
keywords: Central chemoreception; Cytokines; Hypercapnic rebreathing; Interleukin-1β; Respiration