1. ¹VP Chest Institute, University of Delhi, Delhi-110007, India
2. ²RBTB Hospital, Kingsway Camp, Delhi-110007, India

Correspondence: Prof. Mridula Bose, V P Chest Institute, University of Delhi, Delhi-110007, India. Email: mridulabose@hotmail.com

Received 3 November 2003; Accepted 30 January 2004; Published online 28 July 2004.

Abstract

Mycobacterium tuberculosis is an intracellular pathogen that readily survives and replicates in human macrophages. Host cells have developed various mycobactericidal and immunoregulatory mechanisms, such as the production of nitric oxide and inflammatory cytokines to control intracellular replication of M. tuberculosis. Inducible nitric oxide synthase (iNOS) is transcriptionally under the control of IFN- and TNF-. IL-12 provides a crucial link between activated mononuclear phagocytes and T cells by regulating the production of IFN-. In this study, we investigated the production of nitric oxide (NO), TNF- and IL-12 by the peripheral blood monocytes (PB Mn) of patients suffering from multidrug-resistant tuberculosis (MDR-TB). The cells were infected with M. tuberculosis and stimulated with IFN- or activated with mycobacterial subcellular components. The results were compared with those from cases of newly diagnosed TB and healthy controls. Nitric oxide production was significantly depressed in PB Mn from MDR-TB patients. Infected monocytes from newly diagnosed TB patients produced significantly higher levels of NO as compared to those from MDR-TB patients or normal controls. The subcellular fraction of M. tuberculosis-like whole cell lysate (WCL), culture filtrate protein (CFP) and lipoarabinomannan (LAM) induced higher concentrations of NO release in PB Mn from newly diagnosed TB patients as compared to those from MDR-TB patients. Cell culture supernatant from PB Mn assayed at 48 h after infection or stimulation demonstrated significantly depressed release of TNF- and IL-12 from MDR-TB cases as compared to the fresh cases. We observed a definite correlation between nitric oxide release and TNF- production, irrespective of low or high production in MDR-TB or fresh cases, respectively. The present data suggest that peripheral blood monocytes of MDR-TB patients typically show signs of immunosuppression. Whether such immunodepression is the cause or the effect of MDR-TB merits further investigation.