Effect of 1,25 dihydroxyvitamin D3 on intracellular IFN- χ and TNF- α positive T-cell subsets in pulmonary tuberculosis.

Prabhu Anand, S.; Selvaraj, P.; Narayanan, P.R.

Cytokine; 2009; 45; 105–110.

Abstract: We studied the immunomodulatory effect of 1,25(OH) 2 D 3 on sin gle cell expression of IFN- χ and TNF- α cytokines in T cell subsets of pulmonary tuberculosis (PTB) patients (n = 22) and normal healthy subjects (n = 22). Peripheral blood mononuclear cells (PBMCs) were cultured with live Mycobacterium tuberculosis (MTB) with or without 1,25(OH) 2 D 3 (10 -7 M) for 48 h. T cell subsets positive for IFN- χ and TNF- α were enumerated by flow cytometry and the culture supernatants were assayed for both the cytokines using ELISA. In both NHS and PTB patients, a significantly reduced percentage of IFN- χ and TNF- χ expressing CD3+, CD3+CD4+ and CD3+CD8+ T cells were observed in cultures stimulated with live MTB and treated with 1,25(OH) 2 D 3 compared to cultures without 1,25(OH) 2 D 3 (NHS; CD3+ IFN- χ + : p < 0.0001; CD3+TNF- α +: p = 0.0292 and PTB; CD3+ IFN- χ +: p = 0.0292; CD3+ TNF- a +: p = 0.0028). The levels of IFN- c and TNF- a in the culture supernatants of 1,25(OH) 2 D 3 treated cultures were also found to be significantly decreased in both groups (NHS; IFN- χ : p = 0.0001; TNF- α : p < 0.0001) and (PTB; IFN- c : p < 0.0001; TNF- α : p < 0.0001). A positive correlation was observed between IFN- χ and TNF- α expressing CD3+CD8+ T cells in MTB stimulated cultures treated with or without 1,25(OH) 2 D 3 in NHS ( p = 0.0001; p = 0.001, respectively) and PTB patients ( p = 0.002; p = 0.005, respectively). The present study revealed the suppressive effect of 1,25(OH) 2 D 3 on single cell expression of IFN- c and TNF- a by CD3+CD4+ and CD3+CD8+ T cells in pulmonary tuberculosis. This suppressive effect of 1,25(OH) 2 D 3 on proinflammatory and Th1 cytokine positive cells might have a role in reducing inflammation at the site of infection.

Keywords: 1,25 Dihydroxyvitamin D 3 ; Intracellular cytokines; IFN- χ ; TNF- α; Tuberculosis

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