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In contrast to our results in wild-type neonates, blockade of IL-1 receptor in neonates lacking inducible nitric oxide synthase (iNOS) led to significantly increased bacterial loads in the blood and brain. These data indicate IL-1 signaling is protective during NMEC infection in neonates only when iNOS is absent. Collectively, our findings suggest that increased NO production by neonates inhibits IL-1 production, and that this suppresses the protective role of IL-1 signaling in response to NMEC infection. This may indicate a general me