Release of reactive oxygen and nitrogen intermediates from monocytes of patients with pulmonary tuberculosis

Abstract

M. tuberculosis, the aetiological agent of tuberculosis readily infects and multiplies within the macrophages of the host. Macrophage activation is known to occur through a series of stages, which results in the production of biologically active molecules such as the reactive oxygen and nitrogen intermediates. The following study was conducted on 20 patients with pulmonary tuberculosis, before and after initiation of antituberculous therapy, and on 10 normal healthy controls. The macrophages were isolated from peripheral blood of the patients and controls at a concentration of 1 × 10⁶ cells ml^-1. The generation of reactive oxygen intermediates was measured by a chemiluminescence technique. Reactive nitrogen intermediates, were measured following stimulation of macrophages with latex, lipopolysaccharide (LPS) and purified protein derivative-S (PPD-S). Citrulline levels and electron transport chain activity were also determined in the cell cultures. It was observed that there was a significant depression (p<0.05) in the respiratory burst response in the patient group (0.46 × 10³±0.11 cpm per 10⁶ cells) compared with the controls (7.12 × 10³±2.31 cpm per 10⁶ cells). On the other hand, reactive nitrogen intermediates (671.03±2.18 nmol) and citrulline levels (193.07±2.38 nmol) were significantly (p<0.001) higher before initiation of therapy compared with control values (24.36±2.81 and 18.91±2.12 nmol respectively). Their levels declined, during the post-therapy period of 3 months, to 60.81±2.03 and 38.17±2.13 nmol respectively. There was a significant reduction (around 32%) in electron transport chain activity in patients with pulmonary tuberculosis before therapy, which gradually came to normal levels after 3 months of antituberculous therapy. Hence, reactive nitrogen intermediates may have an important role to play in the microbicidal activity of macrophages activated against M. tuberculosis.

Key Words:

• pulmonary tuberculosis
• reactive nitrogen intermediates