Interleukin-1beta suppresses the ventilatory hypoxic response in rats via prostaglandin-dependent pathways.
We investigated the effect of the major inflammatory cytokine interleukin-1beta (IL-1β) on the ventilatory response to hypoxia. The goal was to test the hypothesis that IL-1β impairs the hypoxic ventilatory response in vivo by indirectly inhibiting respiratory neurons in the brainstem via prostaglandins. Thus, IL-1β was delivered by cerebroventricular injection, and the ventilatory hypoxic response was assessed in anesthetized, spontaneously breathing rats pretreated with or without diclofenac, a nonspecific inhibitor of prostaglandin synthesis. We found that the slope of the ventilatory response to hypoxia decreased almost 2-fold from 10.4 ± 3.02 to 4.06 ± 0.86 mL·min-1·(mm Hg)-1(-61%) 90 min after administration of IL-1β (p < 0.05). The slope of tidal volume and mean inspiratory flow also decreased from 0.074 ± 0.02 to 0.039 ± 0.01 mL·(mm Hg)-1(-45%, p < 0.05), and from 0.36 ± 0.07 to 0.2 ± 0.04 mL·s-1·(mm Hg)-1(-46%, p < 0.05), respectively. Pretreatment with diclofenac blocked these effects. Thus, the data indicate that IL-1β degrades the ventilatory hypoxic response by stimulating production of prostaglandin. The increase of cerebral levels of IL-1β, which is induced by the activation of immune cells in the brain, may impair respiratory chemoreflexes.
Respiratory Physiology Lab, Pavlov Institute of Physiology RAS, nab. Makarova, 6, Saint-Petersburg, 199034, Russian Federation.|Respiratory Physiology Lab, Pavlov Institute of Physiology RAS, nab. Makarova, 6, Saint-Petersburg, 199034, Russian Federation.
Nina P
NP
Aleksandrova
Respiratory Physiology Lab, Pavlov Institute of Physiology RAS, nab. Makarova, 6, Saint-Petersburg, 199034, Russian Federation.|Respiratory Physiology Lab, Pavlov Institute of Physiology RAS, nab. Makarova, 6, Saint-Petersburg, 199034, Russian Federation.
Galina A
GA
Danilova
Respiratory Physiology Lab, Pavlov Institute of Physiology RAS, nab. Makarova, 6, Saint-Petersburg, 199034, Russian Federation.|Respiratory Physiology Lab, Pavlov Institute of Physiology RAS, nab. Makarova, 6, Saint-Petersburg, 199034, Russian Federation.
Viacheslav G
VG
Aleksandrov
D000818:Animals; D004008:Diclofenac / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D053583:Interleukin-1beta / Q000494:pharmacology* / Q000627:therapeutic use; D011453:Prostaglandins / Q000378:metabolism*; D012123:Pulmonary Ventilation / Q000187:drug effects*; D051381:Rats; D012119:Respiration / Q000187:drug effects
D053583:Interleukin-1beta; D011453:Prostaglandins; D004008:Diclofenac
breathing; chémoréflexe respiratoire; cytokines; hypoxia; hypoxie; interleukin-1β; interleukine 1β; prostaglandin; prostaglandine; respiration; respiratory chemoreflex; ventilation