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 x 10(6) 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 x 10(3) +/- 0.11 cpm per 10(6) cells) compared with the controls (7.12 x 10(3) +/- 2.31 cpm per 10(6) 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.(ABSTRACT TRUNCATED AT 250 WORDS)