Objectives: Human milk reduces the incidence of necrotizing enterocolitis (NEC). Prior studies have demonstrated that exogenous surfactant protein-A (SP-A) modulates intestinal inflammation, reduces NEC-like pathology in SP-A-deficient (SPAKO) pups, and may contribute to breast milk's immunomodulatory potential. We hypothesize that SP-A is present in milk and impacts inflammatory responses in the terminal ileum of neonatal mice. Methods: Human milk was collected at postpartum days 1-3 and 28. Mouse milk was collected at postpartum days 1-10. SP-A was detected in milk through immunoprecipitation and western blot analysis. The impact of murine wild-type (WT) milk on SPAKO pup ileum was evaluated in a model of intestinal inflammation via cross-rearing experiments. Terminal ileum was evaluated for inflammatory cytokine and toll-like receptor 4 (TLR4) mRNA expression via quantitative real-time RT-PCR. Results: SP-A was detected in human milk and wild type (WT) mouse milk, but not in SPAKO mouse milk. Expression of TLR4, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α was decreased in SPAKO pups reared with WT dams compared to SPAKO pups reared with SPAKO dams, with a peak effect at day of life 14. When inflammation was induced using a lipopolysaccharide-induced model of inflammation, expression of TLR4, IL-1β, IL-6, CXCL-1, and TNF-α was significantly lower in SPAKO pups reared with WT dams compared to SPAKO pups reared with SPAKO dams. Conclusions: SP-A is present in human and murine milk and plays a role in lowering inflammation in murine pup terminal ileum. Both baseline inflammation and induced inflammatory responses are reduced via exposure to SP-A in milk with the effect amplified in inflammatory conditions.

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