Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment

Abstract

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

Deficiency in 25-Hydroxyvitamin D and 30-Day Mortality in Patients With Severe Sepsis and Septic Shock

“…Vitamin D supplementation can also attenuate inflammation and accelerate sputum smear conversion in patients with tuberculosis. 42 These findings on vitamin D and infectious diseases support the immunomodulating role of vitamin D in the pathophysiology of sepsis. 11,12,41,42 The United States Endocrine Society 21 recommends identification of vitamin D deficiency and treatment of the deficiency with vitamin D supplementation.…”

“…42 These findings on vitamin D and infectious diseases support the immunomodulating role of vitamin D in the pathophysiology of sepsis. 11,12,41,42 The United States Endocrine Society 21 recommends identification of vitamin D deficiency and treatment of the deficiency with vitamin D supplementation. In our study, patients who had supplementation with ergocalciferol or cholecaciferol before admission had significantly lower hospital and 90-day mortality than did patients who were not receiving supplementation.…”

Controlled trials of vitamin D, causality and type 2 statistical error

“…2. People who do not supplement may expect to have greater susceptibility to infectious diseases such as tuberculosis (39) and viruses (40)(41)(42) , which have been shown to respond to vitamin D supplementation in clinical trials through improved innate immunity, with increased production of cathelicidin and other natural bacteriocides. 3.…”

Vitamin D and tuberculosis

“…Coussens et al reported an analysis of markers of immune and inflammatory response in a subset of participants from a randomized clinical trial of vitamin D 3 supplementation in culturepositive pulmonary tuberculosis (1). In that trial, the vitamin D intervention did not alter the primary endpoint, time to sputum culture conversion (2), a result that is congruent with that from another randomized controlled trial, in which a clinical severity score was not improved by vitamin D supplementation (3).…”