Interleukin-1 released by blood-monocyte-derived macrophages from patients with leprosy.

In highly purified blood-monocyte-derived macrophages collected from patients with leprosy and from healthy individuals and cultured in vitro with mycobacterial antigens such as Mycobacterium bovis BCG or Mycobacterium leprae, we nonspecifically induced the synthesis of interleukin-1. Normally, all supernatants from cultured macrophages of all subjects tested produced similar amounts of interleukin-1. However, only in patients with lepromatous leprosy, M. leprae, but not BCG, induced high-level synthesis of prostaglandin E2, which acted as a suppressor factor in the mouse thymocyte proliferative assay used to measure the interleukin-1 content of the supernatants. Normal interleukin-1 content of those supernatants was demonstrated by blocking the prostaglandin E2 synthesis by the addition of indomethacin to the medium throughout the experimental procedure. We also tested the efficiency of a combination of BCG and M. leprae in reducing the prostaglandin E2 synthesis, but with the methodology used, we did not observe any beneficial effect of such a combination. These results demonstrate the possible role of M. leprae in the induction of at least one of the suppressive monokines and are additional arguments for the involvement of macrophages in the suppression of the specific cell-mediated immunity to M. leprae observed in lepromatous leprosy.

Cell-mediated immunity in mice treated with Mycobacterium leprae or with macrophages harbouring M. leprae.

Following treatment of BALB/c or C3H/HeN mice in the hind footpads with irradiated Mycobacterium leprae, a marked enhancement of natural killer (NK) activity was observed in cells from the draining popliteal lymph node or from the spleen. NK activity was further enhanced when the treatment consisted of killed M. leprae which had been incorporated into mouse peritoneal macrophages. This effect was noted as early as 2 weeks after treatment and persisted for at least 9 weeks. Lymphoblastic transformation in response to suboptimal doses of the T-cell mitogen transformation in response to suboptimal doses of the T-cell mitogen concanavalin A or to M. leprae antigen was assayed in parallel in cells from the draining popliteal lymph node and from the spleen. In contrast to NK assays, treatment with M. leprae alone moderately altered the response to mitogen. However, there was a prominent enhancement of the T-cell response when treatment consisted of M. leprae-laden macrophages.