SummaryThe production of reactive nitrogen intermediates (RNI) by macrophages is critical to host defence, particularly for exerting the bactericidal and tumoricidal properties. Nitric oxide (NO) were measured in the peripheral blood-derived mono cytes/macrophages of normal and leprosy patients (BTITT and BULL) in the presence and absence of 'tuftsin' as a function of in vitro culture age (on 1, 3, 7 days). Macrophages from both groups of leprosy patients were able to produce NO during the unstimulated state but only BLILL macrophages could be activated by tuftsin to produce significantly high levels of NO. This increase was highest on day 1, then gradually decreased with in vitro culture age. Surprisingly, tuftsin was unable to enhance the NO production in normal macrophages above the basal level. Further, normal and BTITT macrophages had only Cu-Zn derived superoxide dismutase (SOD) activity whereas BULL cultures has Cu-Zn and Mn derived SOD activity. These studies indicate that in BULL cultures: a, apart from tuftsin, some additional signal is required to activate nitric oxide synthase (NOS) gene for NO production; and b, Mn-SOD produced by Mycobacterium /eprae is playing a defensive role against toxic-free radicals. The final outcome of this mechanism is the survival of M. leprae inside the macrophages.Activated macrophages play an important role in host resistance to the development of clinical leprosy and in the limitation of growth of My cobacterium Zeprae. Tuftsin, a tetrapeptide from immunoglobulin G, is an endogenous molecule and a stimulator of phagocytic and microbicidal properties of macrophages has enormous potential clinical implications. I -3 This immunomodulator exerts a differential effect for the phagocytic and microbicidal activity in the monocytes/macrophages derived from peripheral blood of leprosy patients. 4 , 5 It was able to stimulate macrophages of the tuberculoid group for the microbicidal activity but failed to show similar effect(s) in the lepromatous leprosy group. Furthermore, it * Corresponding author 16 0305·75 1 8/97/068016+09 $01 .00 © Lepra Release of reactive nitrogen intermediates of leprosy patients 17 was ineffective in modulating the superoxide anion (02" ) production, but was effective in enhancing the production of hydrogen peroxide (H 2 0 2 ) from the monocyte/macrophages of lepromatous leprosy patients. 6 Studies concerning the mechanism of intracellular killing of pathogens such as leishmania, toxoplasma, M. leprae, M. tuberculosis and trypanosomes using the murine system in vivo and in vitro have suggested that production of reactive nitrogen intermediates (RNI) may be the chief pathway of killing by macrophages stimulated with interferon-gamma (IFN-')') or related cytokines. 7 The activated state of macrophages (as defined by their ability to induce intracellular killing) is related to the release of reactive oxygen as well as nitrogen intermediates and the interaction between them is essential for the final outcome of microbicidal process in the form of lethal ra...
