USE OF GAMMA-INTERFERON IN THE MANUFACTURE OF A MEDICAMENT FOR THE TREATMENT OF LEPROSY

Abstract: The implication of lymphokines in the body's defense mechanism against leprosy makes them suitable phar­ maceutical agents to combat this disease. Either IL-2 or -interferon, separately or together may be administered as a therapeutic agent to an indivdiual suffering from leprosy. When used as anti-leprosy agents the lymphokines may be administered topically at sites of injection or may be adminis­ tered systemically. It has been found that peripheral blood mononuclear cells from 10 out of 10 lepromatous (LL) patients displayed no release of γ-IFN upon stimulation by the specific antigen. In contrast, 6 out of 6 tuberculoid (TT) patients, and borderline tuberculoid (BT) had strong γ-IFN responses. The low respon­ siveness to antigen of some of the borderline lepromatous cases (BL) case suggests that this assay can be helpful in evaluating the prognosis of the disease, suggesting which patients display suppression of cell-mediated responses and would tend to follow the lepromatous course.

Description: Leprosy is a chronic disease caused by Mycobacteria leprae. In some subjects, the disease is disseminated (lepromatous form). In these, widespread lesions present lose infiltrates and the organisms are found in large numbers in skin macrophages. Such individuals have a predominant role in transmitting the disease. The rapid progression of this type of lesion and their heavy bacillary load has been ascribed to deficient T-cell response to the specific antigen, M. leprae, but not to other antigens (Turk, J.L. and Bryuson, A.D.M. Adv. Immunol. 13 : 209-266 (1971); Myrvang, B., Godal, T., Ridley, D.S., Froland, S.S., and Song, Y.K. Clin. Exp. Immun. 14 : 541-553 (1973)). In contrast, subjects with the less severe form of the disease (tuberculoid) develop strong cell-mediated immunity that results in effective killing of bacteria inside macrophages. T-cells from these patients respond strongly to M. leprae antigen. Studies of the lesions of leprosy subjects have revealed that in the lepromatous cases of leprosy the cellular infiltrates are devoid of "helper" T-cells, as identi fied by OKT4/Leu 3a monoclonal antibodies. This is in contrast to tuberculoid patients where a predominance of "helper" T-cells is found (Van Voorhis, W.C., Kaplan G., Sarno, E.N., Horwitz, M.A., Steinman, R.M., Lewis, W.R., Nogueira, N., Hair, L.S., Gattass, C.R., Arrick, B.A. and Cohn, Z.A. New England J. Medicine 307 : 1593-1597 (1982). In the process of macrophage activation, helper-type T-cells generate factors ("lymphokines") which lead to functional changes in macrophage function leading to a microbicidal state (Nogueira, N., Gordon, S. and Cohn Z. J. Exp. Med. 146 : 172 1977; Nogueira, N. and Cohn, Z.A. J. Exp. Med. 148 : 288 1978; Nogueira, N., Chaplan, S. Reesink, M., Tydings J. and Cohn, Z.A. J. Immunol. 128 : 2142 1982). Among other soluble factors, γ -interferon seems to be a large component of such "lymphokine" preparations (waksman, B.H. Biology of the Lmphokines S. Cohen, E. Pck and J.J. Oppenheim, editors Academic Press, New York 585-616 1979). γ -interferon has been shown in a tumor cell mode to copurify with a "macrophage activating factor" (Pace, J.L., Russel, S.W., Schneider, R.D., Altman, A. and Katz, D.H. P.N.A.S. 3782-3786 1983; Wisseman, C.L. Jr. and Waddell, A. J. Exp. Med. 1780-1993 1983): One Document, WO 830 1198 discloses the use of γ -interferon in combination with antibiotics for the treatment of bacterially/fungally contaminated/infected areas. Accordingly, the role of γ -interferon in the progress of leprosy has been studied. Specifically, peripheral blood mononuclear cells from patients with both lepromatous and benign tuberculoid leprosy were examined, in the presence of M. leprae antigen and mitrogens such as Conconavalin A, in terms of capacity for γ -interferon release. Patients with leprosy were examined for the capacity of their peripheral blood mononuclear cells to respond to M . leprae antigen and to mitogens, such as Concanavalin A in terms of γ -interferon release. γ -interferon was measured by anti-viral activity in human foreskin cells infected with encephalo-myocarditis (EMC) virus; γ -interferon was identified by the use of a γ - specific rabbit antibody which specifically neutralized γ -interferon activity.

Claims: Use of γ -interferon for the preparation of a therapeutic drug not containing antibiotics, for the treatment of leprosy.

Inventors: NOGUEIRA, NADIA, STEINMAN, RALPH
Applicants: THE ROCKEFELLER UNIVERSITY
Application year: 1984
Main classification: A61K37
IPC codes: A61K38, G01N33