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Nutritional Immunology

Vitamin A Supplementation Reduces the Monocyte Chemoattractant Protein-1 Intestinal Immune Response of Mexican Children¹

² Department of Nutrition, Harvard School of Public Health, Boston, MA; ³ Hospital Infantil de Mexico Federico Gomez, Mexico City, Mexico; ⁴ Department of Molecular Biomedicine, CINVESTAV, Mexico City, Mexico; ⁵ DePauw University, Greencastle, IN; ⁶ Department of Anthropology, Harvard University, Cambridge, MA; ⁷ University of Texas Medical School, and School of Public Health, Houston, Texas; ⁸ Department of Epidemiology, Harvard School of Public Health, Boston, MA; ⁹ Universidad Autonoma de Queretero, Queretero, Mexico; and ¹⁰ Department of Pediatrics, Harvard Medical School, and Pediatric GI and Nutrition Unit, Massachusetts General Hospital, Boston MA

^* To whom correspondence should be addressed. E-mail: klong{at}hsph.harvard.edu.

The impact of vitamin A supplementation on childhood diarrhea may be determined by the regulatory effect supplementation has on the mucosal immune response in the gut. Previous studies have not addressed the impact of vitamin A supplementation on the production of monocyte chemoattractant protein 1 (MCP-1), an essential chemokine involved in pathogen-specific mucosal immune response. Fecal MCP-1 concentrations, determined by an enzyme-linked immuno absorption assay, were compared among 127 Mexican children 5–15 mo of age randomized to receive a vitamin A supplement (<12 mo of age, 20,000 IU of retinol; 12 mo, 45,000 IU) every 2 mo or a placebo as part of a larger vitamin A supplementation trial. Stools collected during the summer months were screened for MCP-1 and gastrointestinal pathogens. Values of MCP-1 were categorized into 3 levels (nondetectable, <median, median). Multinomial logistic regression models were used to determine whether vitamin A-supplemented children had different categorical values of MCP-1 compared with children in the placebo group. Differences in categorical values were also analyzed stratified by gastrointestinal pathogen infections and by diarrheal symptoms. Overall, children who received the vitamin A supplement had reduced fecal concentrations of MCP-1 compared with children in the placebo group (median pg/mg protein ± interquartile range: 284.88 ± 885.35 vs. 403.39 ± 913.16; odds ratio 0.64, 95% CI 0.42–97, P = 0.03). Vitamin A supplemented children infected with enteropathogenic Escherichia coli (EPEC) had reduced MCP-1 levels (odds ratio = 0.38, 95% CI 0.18–0.80) compared with children in the placebo group. Among children not infected with Ascaris lumbricoides vitamin A supplemented children had reduced MCP-1 levels (OR = 0.62, 95% CI 0.41–0.94). These findings suggest that vitamin A has an anti-inflammatory effect in the gastrointestinal tract by reducing MCP-1 concentrations.

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