Vitamin D status is not associated with inflammatory cytokine levels during experimental human endotoxaemia

Summary Vitamin D has been shown to modulate innate immune responses in vitro and ex vivo ; however, human in‐vivo data are lacking. At high latitudes, seasonal vitamin D deficiency is common due to alternating ultraviolet ( UV) ‐ B radiation exposure. In the present study, we investigated whether levels of 25 hydroxyvitamin D 3 [25( OH ) D 3 ] and its active metabolite 1,25 dihydroxyvitamin D 3 [1,25( OH ) 2 D 3 ] are subject to seasonal variation and whether plasma levels of these vitamin D metabolites correlate with the in‐vivo cytokine response during experimental human endotoxaemia [administration of lipopolysaccharide ( LPS ) in healthy volunteers]. Plasma levels of 25( OH ) D 3 and 1,25( OH ) 2 D 3 were determined in samples obtained just prior to administration of an intravenous bolus of 2 ng/kg LPS (derived from E scherichia coli O :113) in 112 healthy male volunteers. In the same subjects, plasma levels of the inflammatory cytokines tumour necrosis factor ( TNF) ‐α, interleukin ( IL) ‐6 and IL ‐10 were analysed serially after endotoxin administration. Plasma levels of 1,25( OH ) 2 D 3 , but not 25( OH ) D 3 , were subject to significant seasonal variation, with lower levels in autumn and winter. 25( OH ) D 3 and 1,25( OH ) 2 D 3 levels did not correlate with plasma cytokine responses. Furthermore, 25( OH ) D 3 deficient subjects (< 50 nmol/l) displayed an identical cytokine response compared with sufficient subjects. In conclusion, plasma levels of vitamin D are not correlated with the LPS ‐induced TNF , IL ‐6 and IL ‐10 cytokine response in humans in vivo . These findings question the direct role of vitamin D in modulation of the innate immune response.