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Cyclooxygenase pathway in modulation of the ventilatory response to hypercapnia by interleukin-1β in rats
N P Aleksandrova1, G A Danilova1, V G Aleksandrov2
1Laboratory of Respiratory Physiology, Pavlov Institute of Physiology of RAS, nab. Makarova 6, 199034 St.-Petersburg, Russia.
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.
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