Gauree Gupta Konijeti1, Pankaj Arora1, Matthew R Boylan1, Yanna Song1, Shi Huang1, Frank Harrell1, Christopher Newton-Cheh1, Dillon O'Neill1, Joshua Korzenik1, Thomas J Wang1, Andrew T Chan1. 1. Division of Gastroenterology (G.G.K.), Scripps Clinic, La Jolla, California; Scripps Translational Science Institute (G.G.K.), La Jolla, California 92037; Division of Gastroenterology (G.G.K., M.R.B., A.T.C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Cardiology (P.A.), University of Alabama, Birmingham, Alabama 35210; Department of Biostatistics (Y.S., S.H., F.H., D.O., T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (C.N.-C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Gastroenterology (J.K.), Brigham and Women's Hospital, Boston, Massachusetts 02115; and Clinical and Translational Epidemiology Unit (A.T.C.), Massachusetts General Hospital, Boston, Massachusetts 02114.
Abstract
CONTEXT: Although studies have linked vitamin D deficiency with immune-mediated diseases, data demonstrating a direct effect on T-cell function are sparse. OBJECTIVE: Our objective was to determine whether oral vitamin D3 influences T-cell activation in humans with vitamin D deficiency. DESIGN: This was a single-center ancillary study within Vitamin D Therapy in Individuals at High Risk of Hypertension, a double-blind, multicenter, randomized controlled trial. SETTING: This study was undertaken in a single academic medical center. PARTICIPANTS: Adults with vitamin D deficiency and untreated pre- or early stage I hypertension were included. INTERVENTION: In Vitamin D Therapy in Individuals at High Risk of Hypertension, participants were randomized to either low- (400 IU daily) or high- (4000 IU daily) dose oral vitamin D3 for 6 months. In this ancillary study of 38 patients, we measured CD4+ T-cell activation estimated by intracellular ATP release after stimulation of whole blood with plant lectin phytohemagglutinin collected at baseline (pretreatment) and 2-month follow-up. MAIN OUTCOME MEASURE: Determining whether ATP level changes were significantly different between treatment groups was the main outcome measure. RESULTS: Treatment with 4000 IU of vitamin D3 decreased intracellular CD4+ ATP release by 95.5 ng/ml (interquartile range, -219.5 to 105.8). In contrast, 400 IU of vitamin D3 decreased intracellular CD4+ ATP release by 0.5 ng/ml (interquartile range, -69.2 to 148.5). In a proportional odds model, high-dose vitamin D3 was more likely than low-dose vitamin D3 to decrease CD4+ ATP release (odds ratio, 3.43; 95% confidence interval, 1.06-1.11). CONCLUSIONS: In this ancillary study of a randomized controlled trial, we found that high-dose vitamin D3 significantly reduced CD4+ T-cell activation compared to low-dose vitamin D3, providing human evidence that vitamin D can influence cell-mediated immunity.
RCT Entities:
CONTEXT: Although studies have linked vitamin D deficiency with immune-mediated diseases, data demonstrating a direct effect on T-cell function are sparse. OBJECTIVE: Our objective was to determine whether oral vitamin D3 influences T-cell activation in humans with vitamin D deficiency. DESIGN: This was a single-center ancillary study within Vitamin D Therapy in Individuals at High Risk of Hypertension, a double-blind, multicenter, randomized controlled trial. SETTING: This study was undertaken in a single academic medical center. PARTICIPANTS: Adults with vitamin D deficiency and untreated pre- or early stage I hypertension were included. INTERVENTION: In Vitamin D Therapy in Individuals at High Risk of Hypertension, participants were randomized to either low- (400 IU daily) or high- (4000 IU daily) dose oral vitamin D3 for 6 months. In this ancillary study of 38 patients, we measured CD4+ T-cell activation estimated by intracellular ATP release after stimulation of whole blood with plant lectin phytohemagglutinin collected at baseline (pretreatment) and 2-month follow-up. MAIN OUTCOME MEASURE: Determining whether ATP level changes were significantly different between treatment groups was the main outcome measure. RESULTS: Treatment with 4000 IU of vitamin D3 decreased intracellular CD4+ ATP release by 95.5 ng/ml (interquartile range, -219.5 to 105.8). In contrast, 400 IU of vitamin D3 decreased intracellular CD4+ ATP release by 0.5 ng/ml (interquartile range, -69.2 to 148.5). In a proportional odds model, high-dose vitamin D3 was more likely than low-dose vitamin D3 to decrease CD4+ ATP release (odds ratio, 3.43; 95% confidence interval, 1.06-1.11). CONCLUSIONS: In this ancillary study of a randomized controlled trial, we found that high-dose vitamin D3 significantly reduced CD4+ T-cell activation compared to low-dose vitamin D3, providing human evidence that vitamin D can influence cell-mediated immunity.
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