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.