Inflammatory responses of macrophages inhibited by ethanol exposure can be repaired by vitamin D3

Rationale: The immune function of macrophages, can be affected by ethanol. This study examined whether vitamin D3 (1,25D3) could restore the ethanol‐impaired inflammatory response of the human monocytic cell line THP‐1. 1,25D3 is known to increase antimicrobial activity of macrophages. In addition, 1,25D3 promotes monocytes to mature and induces expression of CD14. CD14 together with TLR4 and MD‐2 participates in the recognition of LPS by macrophages. Methods: THP‐1 cells were cultured in the presence or absence of 65 mM ethanol. Prior to the experiments, some of the cell populations were supplemented with 1,25D3. THP‐1 cells were then stimulated with LPS, and TNF production and activation of p38 MAPK were assessed. Results: Ethanol treatment alone reduced TNFα synthesis 3.7 fold (p<0.05). 1,25D3 augmented TNFα production in both untreated and ethanol‐exposed THP‐1 cells (3.3 and 6.6 fold, respectively, p<0.05). 1,25D3‐induced upregulation of TNF levels was accompanied by an additional increase of p38 activation (2.8 and 2.0 fold in untreated and ethanol‐treated cells, respectively). Conclusions: This study shows that 1,25D3 can augment inflammatory responses of human monocytic THP‐1 cells. Moreover, the effect of 1,25D3 on TNF production in ethanol‐treated cells was more pronounced than in untreated cells, suggesting that 1,25D3 may restore ethanol‐induced impairment of inflammatory responses.