PHAGOCYTIC MECHANISM AND ITS PLASMA MODULATORS IN PULMONARY TUBERCULOSIS PATIENTS ON ANTI-TUBERCULOSIS CHEMOTHERAPY AND ZINC SUPPLEMENT B

Abstract

The progression of tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tuberculosis) from latent to drug-sensitive TB (DS-TB) or multi-drug resistant TB (MDR-TB) depends on factors including host-pathogen interactions. The nature and course of these interactions are largely determined by host zinc levels, a function of host immune responses. Clear understanding of these interactions is crucial to identify protection mechanisms, which are not completely elucidated. This study was designed to assess phagocytic mechanism and its plasma modulators in TB patients before and during anti-TB chemotherapy with or without zinc supplementation. Ethical approval (UI/EC/13/0340) was obtained and 160 consenting participants (50 MDR-TB patients, 60 DS-TB patients and 50 controls) were enrolled. The MDR-TB and DS-TB patients were treated with anti-tuberculosis chemotherapy. Thirty DS-TB patients received zinc supplement. Blood sample was collected and plasma obtained from patients at baseline, 2, 4 and 6 months of anti-TB chemotherapy with or without zinc supplement. Phagocytic mechanism [percentage leucocyte migration (%LM) and intracellular killing (%NBT)] were determined by microscopy. Interleukin 6 (IL-6) and 8 (IL-8) were determined using ELISA; superoxide dismutase (SOD), myeloperoxidase (MPO), hydrogen peroxide (H2O2) and nitric oxide (NO) were determined by spectrophotometry. Iron (Fe), zinc (Zn) and copper (Cu) were determined using AAS while vitamins A, C, D and E were determined by HPLC. Data was analysed using Kruskal-Wallis, Mann-Whitney U, Friedman and Wilcoxon signed rank tests at α0.05. In MDR-TB patients, baseline levels of %LM (91.5±0.9 vs 55.0±2.2), IL-6, IL-8 (186.4±29.9 vs 3.7±0.8; 1116.4±198.3 vs 18.9±2.4 pg/mL) and vitamin C (4.80±0.2 vs 3.5±0.7 mg/dL) were significantly higher while MPO (7.5±0.3 vs 8.3±0.3 U/mL), NO (9.2±0.8 vs 14.8±1.3 µmol/L), Fe, Zn and Vitamin A (92.2±2.3 vs 123.3±1.2; 62.6±1.0 vs 118.3±3.1; 49.8±2.6 vs 80.8±6.4 µg/dL) were lower compared with controls. In DS-TB patients, baseline IL-8 (162.6±56.3 vs 18.9±2.4 pg/mL) and MPO (9.3±0.4 vs 8.3±0.3 U/mL) were significantly higher while SOD (0.2±0.0 vs 0.3±0.0 U/mL), H2O2 (269.1±8.3 vs 313.8±7.4 µmol/L), NO (10.3±1.6 vs 14.8±1.3 µmol/L), Zn (81.3±6.3 vs 118.3±3.1 µg/dL), vitamins C and E (0.7±0.0 vs 3.5±0.7; 1.1±0.1 vs 1.7±0.3 mg/dL) were lower compared with controls. At 2 months of anti-TB chemotherapy compared with baseline, MPO (11.1±0.3 vs 9.6±0.3 U/mL) was significantly increased in DS-TB patients on anti-TB chemotherapy alone while SOD (0.2±0.0 vs 0.1±0.0 U/mL), MPO (17.5±1.0 vs 9.0±0.7 U/mL) and NO (25.7±2.4 vs 20.7±1.8 µmol/L) were increased in DS-TB patients on chemotherapy and zinc supplement. At 4 months of anti-TB chemotherapy, MPO (18.7±1.2 vs 9.0±0.7 U/mL) and NO (26.8±2.2 vs 20.7±1.8 µmol/L) were significantly increased in DS-TB patients on anti-TB chemotherapy and zinc supplement compared with baseline. At 6 months of anti-TB chemotherapy in DS-TB patients compared with baseline, H2O2 and NO (372.9±6.1 vs 316.7±7.9; 14.7±1.4 vs 12.0±1.3 µmol/L) were 4 increased in patients on anti-TB chemotherapy alone while MPO (20.2±1.3 vs 9.0±0.7 U/mL) increased in patients on anti-TB chemotherapy and zinc supplement. Zinc supplementation with anti-tuberculosis chemotherapy improved phagocytic mechanism and its plasma modulators in TB patients from 2 months of treatment