Vitamin A supplementation modifies the association between mucosal innate and adaptive immune responses and resolution of enteric pathogen infections.
BACKGROUND
The efficacy of vitamin A supplementation on diarrheal disease morbidity may reflect the divergent effects that supplementation has on pathogen-specific immune responses and pathogen-specific outcomes.


OBJECTIVE
We examined how vitamin A supplementation modified associations between gut-cytokine immune responses and the resolution of different diarrheal pathogen infections.


METHODS
Stools collected from 127 Mexican children who were 5-15 mo old and enrolled in a randomized, placebo-controlled vitamin A supplementation trial were screened for enteropathogenic Escherichia coli (EPEC), enterotoxigenic E. coli (ETEC), and Giardia lamblia. Fecal concentrations of interleukin (IL)-6, IL-8, IL-4, IL-5, IL-10, monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were measured by using an enzyme-linked immunosorbent assay. Hazard models that incorporated categorized cytokine variables (ie, nondetectable, less than the median of detectable concentrations, and at least the median of detectable concentrations) were fit to the length of pathogen infections stratified by treatment group.


RESULTS
Vitamin A-supplemented children with fecal MCP-1 or IL-8 concentrations less than the median of detectable concentrations and IL-10 concentrations of at least median concentrations had longer durations of EPEC infection than did children in the placebo group. In supplemented children, detectable fecal TNF-α or IL-6 concentrations were associated with shorter ETEC infection durations, whereas MCP-1 concentrations of at least the median were associated with longer infection durations. Children in this group who had IL-4, IL-5, or IFN-γ concentrations of at least median detectable concentrations had shorter durations of G. lamblia infection.


CONCLUSIONS
The effect of supplementation on associations between fecal cytokine concentrations and pathogen infection resolution depends on the role of inflammatory immune responses in resolving specific pathogen infections.
Nutrition, Environmental Health, Disease and Injury Control Unit, School of Population Health, University of Queensland, Queensland, Australia. k.long@uq.edu.au
Kurt Z
KZ
Long
José Ignacio
JI
Santos
Jorge L
JL
Rosado
Teresa
T
Estrada-Garcia
Meredith
M
Haas
Abdullah
A
Al Mamun
Herbert L
HL
DuPont
Nanda N
NN
Nanthakumar
D056704:Adaptive Immunity / Q000187:drug effects; D016207:Cytokines / Q000032:analysis; D003968:Diarrhea, Infantile / Q000188:drug therapy* / Q000276:immunology*; D019587:Dietary Supplements; D004755:Enterobacteriaceae / Q000187:drug effects / Q000302:isolation & purification*; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology; D054308:Enteropathogenic Escherichia coli / Q000187:drug effects / Q000302:isolation & purification; D054307:Enterotoxigenic Escherichia coli / Q000187:drug effects / Q000302:isolation & purification; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005260:Female; D016829:Giardia lamblia / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D007113:Immunity, Innate / Q000187:drug effects; D018928:Immunity, Mucosal / Q000187:drug effects; D007223:Infant; D008297:Male; D008800:Mexico; D016016:Proportional Hazards Models; D014801:Vitamin A / Q000627:therapeutic use*
D016207:Cytokines; D014801:Vitamin A
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