Exogenous vitamin D inhibits human pro-inflammatory cytokine responses to TLR-4L but not TLR-8L innate immune activation (P6331)

Abstract

Abstract Population health studies demonstrate that insufficient/deficient Vitamin D status is strongly associated with increased upper respiratory tract infections. As low vitamin D status is widespread, it is imperative to understand the roles it plays during an immune response. Here we determine the effects of active vitamin D (1,25(OH)2D3) on peripheral blood mononuclear cells (PBMC) cytokine responses elicited by bacterial or viral ligands and explore mechanisms by which vitamin D regulates innate immune responses. Results: PBMC stimulated with TLR-4L and exogenous 1,25(OH)2D3 exhibited decreased pro-inflammatory cytokine production; whereas cultures stimulated with TLR-8L did not exhibit alterations in cytokine production patterns in the presence of supplemental 1,25(OH)2D3. 1,25(OH)2D3 alone slightly reduced TLR-4 but decreased TLR-8 by >75%. Moreover, while TLR-4 ligand stimulation had no effect on VDR levels, TLR-8L stimulation reduced VDR mRNA by 60% (p<0.005). Conclusions: Exogenous 1,25(OH)2D3 markedly reduces inflammatory cytokine production elicited by TLR-4 but not by TLR-8 or RSV activation. TLR-8L strikingly reduce VDR while 1,25(OH)2D3 reduces viral PRR expression, resulting in a synergistic decrease in the capacity of viral stimulated cells to have responses modulated by exogenous vitamin D. The results suggest a need for closer examination of the benefits of exogenous vitamin D supplementation in bacterial versus viral infection.