Mycobacterium leprae mediated stimulation of macrophages from leprosy patients and hydrogen peroxide production.

Macrophages cultured from the peripheral blood of normal individuals, tuberculoid leprosy patients and long-term-treated, bacteriologically negative lepromatous leprosy patients are able to release hydrogen peroxide on stimulation with Mycobacterium leprae. Macrophages from lepromatous leprosy patients who are bacteriologically positive produce considerably lower levels of hydrogen peroxide, even though stimulation of these cells with Mycobacterium leprae is definitely demonstrable. This differential stimulation of macrophages appears to be largely specific to Mycobacterium leprae. There is also a good indication that decreased stimulation of macrophages from positive patients could be due to an after-effect of infection. It is possible that while other factors aid survival of Mycobacterium leprae in the macrophages, hydrogen peroxide may not be as effective in the killing of the bacteria in infected patients as it would be, perhaps, in other infections.

Superoxide production from macrophages of leprosy patients after stimulation with Mycobacterium leprae.

The macrophages from peripheral blood of normal healthy individuals respond to live or killed Mycobacterium leprae by producing superoxide. On the other hand, the macrophages from bacteriologically positive (B + LL) or long term treated bacteriologically negative (B – LL) and tuberculoid leprosy patients are unable to produce superoxide when stimulated with live Mycobacterium leprae. While killed Mycobacterium leprae induce superoxide with the cells from tuberculoid and B(–)LL patients, cells from B(+)LL patients fail to respond. The deficiency in B(–)LL patients to produce superoxide appears to be specific with Mycobacterium leprae and the defect can be counteracted by the addition of colchicine. These observations indicate a preexisting membrane disposition which does not favour superoxide production. A similar situation is seen in the cells from tuberculoid leprosy patients. Thus it appears that both cured and active lepromatous leprosy patients have defective macrophages, unable to respond to live Mycobacterium leprae to produce superoxide anion, in contrast to the situation with the cells from normal healthy individuals.