Markers of innate immune function are associated with vitamin a stores in men

Abstract

Recommendations for vitamin A intake and liver stores are based on maintaining normal vision. We propose that higher levels may be required to maintain normal innate immune function. To test this hypothesis, we conducted an 8-wk residential study among 36 healthy Bangladeshi men with low vitamin A stores. Subjects were randomized to receive vitamin A (240 mg in 4 doses) or placebo during study wk 2 and 3. They received 2 vaccines during wk 5 and vitamin A stores were estimated by isotopic dilution at wk 8. The serum concentration of the chemokine interferon-gamma-induced protein 10, a component of T-helper 1 (Th1) response, increased significantly after supplementation and was positively and significantly associated with vitamin A stores. Blood concentrations of natural killer (NK) and NK T-cells, which have anticancer and antiviral activity, were positively associated with stores (P < 0.05), as was monocyte oxidative burst (P < 0.05), a marker of bacterial killing ability. However, serum interleukin (IL)-6 and IL-17, cytokines that regulate the antibacterial Th17 response, were significantly and negatively associated with stores, as was production of the regulatory cytokine IL-10 by whole-blood cultures stimulated with bacterial lipopolysaccharide. In summary, vitamin A stores were positively associated with several measures of innate immune activity across a broad range of stores, suggesting that vitamin A enhances protection against diverse pathogens even at concentrations above those needed to maintain normal vision. The negative association of stores with serum IL-6 and IL-17 suggests that not all protective responses are similarly enhanced by vitamin A.

FIGURE 1

Spearman correlation between whole body vitamin A store and measures of innate immunity, n = 33. (A) Absolute counts (per liter of whole blood) of leukocytes primarily involved in the innate immunity. (B) Intensities of PMA (50 μg/L) and 1 × 10⁷ E. coli-induced ROS as measure of oxidative burst activity and intensities of 1 × 10⁷ E. coli-induced phagocytic activities of monocytes and granulocytes in heparinized blood. (C) Inflammatory cytokine responses in the culture supernatant of 20% whole blood stimulated by 1 mg/L LPS for 24 h. (D) Serum cytokine, chemokine, and acute phase protein responses. Very similar correlation coefficients were seen when these immune response variables were correlated with estimated liver vitamin A stores (data not shown). *P < 0.05.

FIGURE 2

Change in serum cytokine, chemokine, and acute phase protein concentrations in response to supplementation and vaccination. Legends in horizontal time lines. (A) Presupplementation, (B) 1 wk postsupplementation, (C) 1 wk postvaccination, and (D) 1 mo postvaccination. Between-group differences at B; ^a P < 0.05 (Table 3). Between-group difference at B, C, and D; ^bP < 0.05. Within-group difference at B, C, and D; ^c P < 0.05.

FIGURE 3

Relationship between liver vitamin A concentrations and logical groupings of innate immune measures (n = 33). (A) E .coli-induced oxidative burst and phagocytic activity of monocytes and granulocytes. (B) Absolute counts of NK and NKT cells per liter of whole blood. (C) Serum IL-6 and IL-17 concentrations. The Z-score–normalized responses for each group were plotted and the break-point estimates obtained from the 2-phase segmental linear regression model as described in “Materials and Methods.”