Cyclooxygenase pathway in modulation of the ventilatory response to hypercapnia by interleukin-1ß 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-1ß (IL-1ß) 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-1ß 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-1ß. In contrast, the basal level of lung ventilation increased after the elevation of IL-1ß in CSF. Diclofenac pretreatment eliminated these respiratory effects of IL-1ß. The data indicate that the ability of IL-1ß to enhance basal ventilation and to reduce the ventilatory hypercapnic response is mediated by the COX pathway.