Background-Vitamin D was used to treat tuberculosis in the pre-antibiotic era, and its metabolites induce antimycobacterial immunity in vitro. Clinical trials investigating the effect of adjunctive vitamin D on sputum culture conversion are lacking.

Calcidiol, the major circulating metabolite of vitamin D, supports induction of pleiotropic antimicrobial responses in vitro. Vitamin D supplementation elevates circulating calcidiol concentrations, and thus has a potential role in the prevention and treatment of infection. The immunomodulatory effects of administering vitamin D to humans with an infectious disease have not previously been reported. To characterize these effects, we conducted a detailed longitudinal study of circulating and antigen-stimulated immune responses in ninety-five patients receiving antimicrobial therapy for pulmonary tuberculosis who were randomized to receive adjunctive high-dose vitamin D or placebo in a clinical trial, and who fulfilled criteria for per-protocol analysis. Vitamin D supplementation accelerated sputum smear conversion and enhanced treatment-induced resolution of lymphopaenia, monocytosis, hypercytokinaemia, and hyperchemokinaemia. Administration of vitamin D also suppressed antigen-stimulated proinflammatory cytokine responses, but attenuated the suppressive effect of antimicrobial therapy on antigenstimulated secretion of IL-4, CC chemokine ligand 5, and IFN-α. We demonstrate a previously unappreciated role for vitamin D supplementation in accelerating resolution of inflammatory responses during tuberculosis treatment. Our findings suggest a potential role for adjunctive vitamin D supplementation in the treatment of pulmonary infections to accelerate resolution of inflammatory responses associated with increased risk of mortality.adjunctive therapy | immunomodulation | antimicrobial peptides | matrix metalloproteinases | steroid hormones

Vitamin D deficiency is associated with susceptibility to tuberculosis (TB) in HIV-uninfected people in Europe, but it is not known whether such an association exists among HIV-infected people in subtropical Africa. We conducted a cross-sectional study to determine whether vitamin D deficiency was associated with susceptibility to active TB in and HIV-infected (n = 174) black Africans in Cape Town, South Africa. We also investigated whether there was evidence of seasonal variation in vitamin D status and TB notifications in this setting over an 8-y period.nmol/L) was present in 232 (62.7%) of 370 participants and was associated with active TB in both HIV-uninfected (odds ratio = 5.2, 95% confidence interval: 2.8-9.7; P < 0.001) and HIV-infected (odds ratio = 5.6, 95% confidence interval: 2.7-11.6; P < 0.001) people. We have previously reported that vitamin D deficiency is associated with susceptibility to TB in London and that this association is modified by polymorphisms in the vitamin D receptor and vitamin D binding protein (8,9). We have also shown that in vivo vitamin D supplementation enhances immunity to mycobacteria both in healthy people (10) and in a genetically defined subgroup of patients with active TB (11). Reports of seasonal variation in the prevalence of vitamin D deficiency (12) and TB incidence (13) in the United Kingdom provide further evidence that low vitamin D status may compromise antimycobacterial immunity in this setting.The prevalence of profound vitamin D deficiency among TB patients in tropical Africa is much lower than in Europe [reported in 0.3-11.2% of patients with TB in tropical Africa (14-17) vs. 64-84% of patients with TB in ]. The prevalence of vitamin D deficiency in TB patients with and without HIV infection in subtropical Africa has not previously been reported. There is particularly good reason to investigate this question in Cape Town, South Africa, because TB incidence in Cape Town is higher than elsewhere in South Africa (21) and the ability of sunlight to synthesize vitamin D is compromised during the winter in Cape Town (latitude 33°south) but not in Johannesburg (latitude 26°south) (22). We therefore conducted an observational study to determine whether vitamin D deficiency is associated with susceptibility to active TB in HIVinfected and HIV-uninfected adults in Cape Town and to investigate whether there is evidence of seasonal variation in vitamin D status and TB notifications in this setting.

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