Vitamin A Modifies the Intestinal Chemokine and Cytokine Responses to Norovirus Infection in Mexican Children1,2

Abstract

AbstractVitamin A supplementation is associated with divergent clinical norovirus (NoV) outcomes in Mexican children. Fecal cytokine concentrations following NoV genogroup infections among 127 Mexican children 515 mo old enrolled in a randomized, double-blind, placebo-controlled, vitamin A supplementation trial were determined to clarify the role the gut immune response plays in these associations. Stools collected from supplemented children [20,000 IU retinol (3.3 IU = 1 g retinol) for children < 12 mo of age; 45,000 IU for children = 12 mo] or children in the placebo group were screened for NoV genogroups I (GI) and II (GII). Monocyte chemoattractant protein-1 (MCP-1), TNFa, IL-5, IL-6, IL-8, IL-4, IFN?, and IL-10 fecal concentrations were also determined. Differences in cytokine levels between the 2 groups following GI and GII infections were determined using ordered logistic regression models. MCP-1 and IL-8 levels were greater among GI- and GII-infected children, respectively, compared with uninfected children, whereas IL-5 levels were greater following both genogroup infections. MCP-1, IL-8, and IL-6 fecal levels were reduced among supplemented children with GII-associated diarrhea compared with the placebo group. Vitamin Asupplemented, GII-infected children had reduced MCP-1 and TNFa levels compared with GII-infected children in the placebo group (P-interaction = 0.02 and 0.03, respectively). Supplemented children with GI-associated diarrhea had higher TNFa and IL-4 levels compared with children in the placebo group with diarrhea (P-interaction = 0.02 and 0.02, respectively). The divergent effects of supplementation on NoV outcomes may result from the different effects vitamin A has on the genogroup-specific immune responses.