A major inflammatory cytokine IL-1β inhibits the ventilatory response to hypoxia

Abstract

IL-1β is a major inflammatory cytokine produced during an acute phase immune response to infection and inflammation. The systemic level of inflammatory cytokines has been reported to be increased in many respiratory diseases such as asthma, chronic obstructive pulmonary disease or sleep apnea.Previous studies have shown that the carotid body (CB) express interleukin (IL)-1 receptor type I. It is known that CB is the main arterial chemoreceptor that mediates reflex hyperventilation during hypoxia. The aim of the present study was to examine the hypothesis that elevation of pro-inflammatory cytokine level in blood may modulate the ventilatory hypoxic response. The experiments were performed on tracheostomized anaesthetized rats. Human recombinant interleukin-1β (IL-1β) was administrated in the femoral vein in an amount of 500 ng dissolved in 1 ml of saline. The ventilatory hypoxic response was measured by using rebreathing techniques before and after injection of ether saline (placebo) or IL-1β. Using a method of rebreathing with hypoxic gas mixture we have shown that the slope of the ventilatory, tidal volume and mean inspiratory flow responses to hypoxia decreased at 40 min after administration of IL-1β. When the resting breathing basal level of lung ventilation in contrary increased after elevate of IL-1β level in the blood. We concluded that the elevation of inflammatory cytokine level in blood intensifies ventilation during the resting breathing but weakens ventilatoryresponse to hypoxia that suggests participation of inflammatory cytokines in mechanisms of central breathing control and central chemoreception. The study was supported by Russian Science Foundation (RScF) grant No. 15-15-00119.