DHARMENDRA ANTIGEN BUT NOT INTEGRAL MYCOBACTERIUM-LEPRAE IS AN EFFICIENT INDUCER OF IMMUNOSTIMULANT CYTOKINE PRODUCTION BY HUMAN MONOCYTES,AND MYCOBACTERIUM-LEPRAE LIPIDS INHIBIT THE CYTOKINE PRODUCTION

Killed integral Mycobacterium leprae, Mitsuda antigen, and chloroform- treated M. leprae, Dharmendra antigen (Dh-Ag), have been used for the classification of leprosy patients based on cell-mediated immunity. He at-killed M. leprae also are used as a component of the Convit vaccine . Human blood monocytes were stimulated with M. leprae or Dh-Ag and th eir cytokine-inducing ability was compared. Monocytes were cultured in the presence of fresh human serum because the efficacy of cytokine in duction and the phagocytosis of M. leprae have been shown to be optima l in the presence of fresh serum. M. leprae and Dh-Ag were equally pha gocytosed by monocytes Dh-Ag was more potent than M. leprae in the ind uction of immunostimulatory/proinflammatory cytokines, interleukin-1 ( IL-1) IL-6 and tumor necrosis factor (TNF). In contrast, a comparable level of IL-1ra, an immunosuppressive cytokine, was induced by M. lepr ae and Dh-Ag. The lipids extracted from M. leprae induced none of thes e cytokines by monocytes. Nevertheless, when monocytes were pretreated with the lipids followed by stimulation with Dh-Ag, productions of IL -1, IL-6 and TNF were all inhibited in a dose-dependent manner. Howeve r, the lipids did not inhibit the cytokine production induced by other stimuli, including BCG and lipopolysaccharide. Moreover the lipids di d not affect the production of IL-1ra. These results suggest that the lipids from M. leprae are responsible for the poor cytokine-inducing a bility of M. leprae, thus favoring their infection. These results also suggest that Dh-Ag rather than integral M. leprae may be useful as a vaccine candidate because Dh-Ag is able to induce a large amount of cy tokines from monocytes.