High-level dietary vitamin A enhances T-helper type 2 cytokine production and secretory immunoglobulin A response to influenza A virus infection in BALB/c mice

Vitamin A supplementation during acute pneumonia has not improved recovery in most human clinical trials. We hypothesize that high vitamin A intake may decrease the production of T-helper type-1 (Th1) cytokines and thereby inhibit antiviral responses. Such decreases might impair recovery from viral respiratory infections, We thus examined the effect of three interventions on viral pneumonia: 1) a high level vitamin A [250,000 IU/kg diet or 75,000 retinol equivalents (RE)/kg], or 2) control diet (4000 IU/kg diet or 1200 RE/kg) given before and during infection, and 3) initiating the high level diet upon infection to simulate the adjuvant therapy used in clinical trials. No difference was seen among the interventions in severity of disease (weight loss, lung virus titers and survival). However, both the high level diet group and the group in which vitamin A was increased at the time of infection had greater salivary immunoglobulin (Ig)A responses (geometric means, 166 and 105 mu g/L, respectively) than did the control group (59 mu g/L) (P = 0.0019). In contrast, the serum IgG response was higher in the control group (324 +/- 158 mg/L) than in the high level group (225 +/- 95 mg/L) (P = 0.028), although it did not differ from the group in which the diet was changed upon infection (230 +/- 163 mg/L) (P = 0.084). The production of interferon-gamma (IFN-gamma), a Th1 cytokine, was lower in the high level diet group (median, 0.153 mu g/L) compared with the control group (median, 0.839 mu g/L) (P = 0.014), whereas the production of interleukin-10 (IL-10), a Th2 cytokine, was higher with the high level diet (median, 0.304 mu g/L) than with the control (median, 0.126 mu g/L) (P = 0.022). This change in the Th1/Th2 pattern was not sufficient to affect recovery from viral pneumonia but may account for the increased IgA and decreased IgG responses seen with high level dietary vitamin A in this study. These data reinforce the lack of utility of vitamin A in treating acute pneumonia in children and suggest that high dose vitamin A supplements may enhance Th2-mediated immune responses, which are particularly beneficial in the case of extracellular bacterial and parasitic infections and IgA-mediated responses to mucosal infections.