isotretinoin and Tuberculosis

Mycobacterium tuberculosis (Mtb) survives and proliferates within the main cells of the innate immune system, macrophages. The goal of our study was to investigate the immunostimulatory effects of 13-cis retinoic acid (RA) and chicoric acid (CA) in human U937 macrophages against H37Ra Mtb infection by evaluating its potential role in the cell surface expression of HLA-DR, CD14 molecules as well as nitric oxide (NO) production and prevention of the Mtb growth within macrophages. In this study, we investigated the effects of 13-cis RA and CA on Mtb-infected macrophages using flowcytometry and Griess methods, respectively. Moreover, inhibitory effect of 13-cis RA and CA on Mtb growth within macrophages were assessed using colony-forming unit. 13-Cis RA and CA enhanced the cell surface expression of HLA-DR and CD14 molecules on U937 macrophages and prevented the growth of Mtb within macrophages. In addition, 13-cis RA and CA, have increased NO generation compared to untreated control macrophages, significantly (p < 0.001). Both drugs have a significant inhibitory effect on Mtb growth but CA at the highest concentration was more potent than 13-cis RA (p < 0.05). The results of our study showed that infected U937 macrophages treated with 13-cis RA and CA represented significant increases in NO production, CD14 and HLA-DR expression and also prevents intracellular survival of Mtb. Therefore, 13-cis RA and CA may have a significant therapeutic approach in the control of Mtb infection.

Topics: Caffeic Acids; Colony Count, Microbial; HLA-DR Antigens; Humans; Immunization; Isotretinoin; Lipopolysaccharide Receptors; Macrophages; Mycobacterium tuberculosis; Nitric Oxide; Succinates; Tuberculosis; U937 Cells; Up-Regulation

The aim of this study was to estimate the concentration of cholecalciferol and 13-cis-retinoic acid (RA) in the plasma and pleural fluid of patients with tuberculosis (TB) against controls.. Plasma levels of cholecalciferol and 13-cis-RA were measured in 22 patients with TB and healthy controls and their pleural fluids levels were measured in 6 TB patients and diseased controls by established high-performance liquid chromatography-based procedure.. Cholecalciferol levels in plasma and pleural fluid of patients with TB and healthy controls were 67.45 (10.71) nmol/L and 21.40 (8.58) nmol/L compared with 117.43 (18.40) nmol/L (P < 0.001) and 94.73 (33.34) nmol/L (P = 0.0049), respectively. 13-cis-RA level in the plasma of patients with TB and healthy controls were 1.51 (0.72) nmol/L and 6.67 (0.81) nmol/L (P < 0.001), respectively. 13-cis-RA was not detectable in pleural fluid. The levels of both the agents were lower in patients with TB than in controls.. It was observed that in patients with TB there is a combined deficiency of cholecalciferol and 13-cis-RA compared with healthy volunteers. Because cholecalciferol and 13-cis-RA are in equilibrium with active ingredients of vitamins A and D, we feel that there is a combined deficiency of these vitamins in patients with TB. There is an evidence that concomitant vitamin A and D supplementation can kill intracellular Mycobacterium tuberculosis in vitro. Therefore, the observations made in this study can pave the path for a trial of combined supplementation of available formulations of vitamin A and D (cholecalciferol and 13-cis-RA) for novel anti-tubercular drug therapy. Because such an approach is host-based it has potential to treat even multidrug-resistant and extensively drug-resistant forms of TB.

Topics: Adolescent; Adult; Aged; Case-Control Studies; Cholecalciferol; Dietary Supplements; Drug Resistance, Multiple, Bacterial; Female; Humans; Isotretinoin; Male; Middle Aged; Mycobacterium tuberculosis; Tuberculosis; Vitamin A Deficiency; Vitamin D Deficiency; Young Adult