Vitamin A supplementation modifies associations between intestinal immune responses and enteric pathogen infections among Mexican children.

The effect of vitamin A supplementation on childhood infectious disease outcomes may result from the regulatory effect it has on the pathogen‐specific immune response. The associations between intestinal cytokine responses and diarrheal pathogen infection durations were compared between children receiving vitamin A or a placebo in a randomized clinical trial carried out in Mexico City. Parametric hazards models incorporating categorized variables for TNF‐α, IFN‐γ and IL‐4 were fit to overall durations of enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), and G. lamblia infections and durations stratified by treatment arm. Overall, increased TNF‐α levels were associated with increased EPEC infection durations (HR 0.28 95% CI 0.09–0.84); increased IFN‐γ levels were associated with reduced EPEC durations and increased G. lamblia durations (HR 3.21 95% CI 1.24–8.29 and HR 0.12 95% CI 0.03–0.44, respectively); and increased IL‐4 levels were associated with increased EPEC durations but reduced ETEC durations (HR 0.01 95% CI 0.00–0.10 and 2.67 95% CI 1.08–6.60, respectively). Vitamin A eliminated the association between increased TNF‐α levels and increased EPEC durations and the association between increased IFN‐γ/IL‐4 levels and increased ETEC and G. lamblia durations. Vitamin A reduces the negative effects that TNF‐α and IFN‐γ have on the resolution of non‐invasive enteric infections.