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

Interleukin 1-beta (IL-1 beta) is a cytokine that modulates breathing when applied systemically or directly into the brain. IL-1 beta is expressed, along with its receptors, in IL-1 beta-sensitive respiratory-related circuits, which likely include the inspiratory rhythm generator (the preBotzinger complex, preBotC). Thus, considering that IL-1 beta might directly modulate preBotC function, we tested whether IL-1 beta and its endogenous antagonist IL1Ra modulate inspiratory rhythm generation in the brainstem slice preparation containing the preBotC. We found that IL-1 beta reduces, in a concentration-dependent manner, the amplitude of the fictive inspiratory rhythm generated by the preBotC, 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-1 beta 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-1 beta modulates breathing by directly modulating the inspiratory rhythm generation. This modulation could contribute to the respiratory response to inflammation in health and disease.