title: Vitamin A modifies the intestinal chemokine and cytokine responses to norovirus infection in Mexican children.
abstract: Vitamin A supplementation is associated with divergent clinical norovirus (NoV) outcomes in Mexican children. Fecal cytokine concentrations following NoV genogroup infections among 127 Mexican children 5-15 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 μg 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), TNFα, IL-5, IL-6, IL-8, IL-4, IFNγ, 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 A-supplemented, GII-infected children had reduced MCP-1 and TNFα 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 TNFα 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.
authors.affiliation: The University of Queensland, School of Population Health, Nutrition, Environmental Health and Disease and Injury Control Unit, Herston, Qld 4006, Australia. k.long@uq.edu.au
authors.forename: Kurt Z
authors.initials: KZ
authors.lastname: Long
authors.forename: Coralith
authors.initials: C
authors.lastname: Garcia
authors.forename: GwangPyo
authors.initials: G
authors.lastname: Ko
authors.forename: Jose I
authors.initials: JI
authors.lastname: Santos
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al Mamun
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Rosado
authors.forename: Herbert L
authors.initials: HL
authors.lastname: DuPont
authors.forename: Nanda
authors.initials: N
authors.lastname: Nathakumar
mesh_terms: D056704:Adaptive Immunity; D017250:Caliciviridae Infections / Q000276:immunology / Q000517:prevention & control*; D018925:Chemokines / Q000032:analysis* / Q000276:immunology; D016207:Cytokines / Q000032:analysis* / Q000276:immunology; D019587:Dietary Supplements; D004311:Double-Blind Method; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005260:Female; D005759:Gastroenteritis / Q000276:immunology / Q000517:prevention & control; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D056747:Immunomodulation; D007223:Infant; D007422:Intestines / Q000276:immunology* / Q000382:microbiology; D008297:Male; D008800:Mexico; D029322:Norovirus / Q000145:classification / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D014801:Vitamin A / Q000627:therapeutic use*; D014802:Vitamin A Deficiency / Q000276:immunology / Q000517:prevention & control
chemical_list: D018925:Chemokines; D016207:Cytokines; D014801:Vitamin A