Interleukin 1-beta but not the interleukin-1 receptor antagonist modulates inspiratory rhythm generation in vitro

Interleukin 1-beta (IL-1β) is a cytokine that modulates breathing when applied systemically or directly into the brain. IL-1β is expressed, along with its receptors, in IL-1β-sensitive respiratory-related circuits, which likely include the inspiratory rhythm generator (the preBötzinger complex, preBötC). Thus, considering that IL-1β might directly modulate preBötC function, we tested whether IL-1β and its endogenous antagonist IL1Ra modulate inspiratory rhythm generation in the brainstem slice preparation containing the preBötC. We found that IL-1β reduces, in a concentration-dependent manner, the amplitude of the fictive inspiratory rhythm generated by the preBötC, which is prevented by IL1Ra. Only a negligible effect on the rhythm frequency was observed at one of the concentrations tested (10 ng/mL). In sum, these findings indicate that IL-1β modulates respiratory rhythm generation. In contrast, IL1Ra did not produce a major effect but slightly increased burst amplitude regularity of the fictive respiratory rhythm. Our findings show that IL-1β modulates breathing by directly modulating the inspiratory rhythm generation. This modulation could contribute to the respiratory response to inflammation in health and disease.