Immunochemotherapy with interferon-gamma and multidrug therapy for multibacillary leprosy

Treatment for multibacillary leprosy is presently performed with a multidru g therapy (MDT) scheme maintained for 2 years. Leprosy treatment however ca n benefit from the reduction of length. The lack of interferon-gamma (IFN-g amma) production by lepromatous leprosy (LL) patients' lymphocytes lead us to use this cytokine in the treatment of multibacillary leprosy associated with MDT in the treatment of multibacillary leprosy, and monitor several cl inical and immunological parameters during the course of treatment. A total of 20 multibacillary leprosy patients were evaluated, 10 treated with MDT alone, and 10 treated with MDT + 10 daily doses of 2 x 10(6) international units (IU) of recombinant human IFN-gamma/m(2) followed by 10 daily doses o f 10(7) IU IFN-y/m(2), intramuscularly, during the first 20 days of MDT. IF N-gamma was well tolerated and did not cause any increase in the rate of le prosy reactions development during treatment. Decrease of bacillary load, f all of anti-Mycobacterium leprae IgG serum antibodies, changes of histologi cal pattern, as well as changes in lymphocyte proliferation assay in respon se to mitogens (PHA or PWM), M. leprae antigen or PPD was similar in both g roups of patients. Among several soluble immunological markers measured bef ore and 30 days after beginning of treatment, levels of soluble IL-2R recep tor increased in patients treated with MDT plus IFN-gamma whereas decreased in patients treated with MDT alone. Soluble ICAM-1 levels decreased in the MDT group but did not change in the MDT + IFN-gamma treated patients. Solu ble CD4 and soluble CD8 markers did not change significantly in either grou p of patients. Neopterin, a marker of macrophage activation, increased in a ll but one patient treated with MDT + IFN-gamma but in none treated with MD T alone, indicating that IFN-gamma was active in vivo. Our findings indicat e that despite being able to promote macrophage activation in multibacillar y leprosy patients a short course of systemically administered IFN-gamma is not able to change the clinical course of a long standing disease such as leprosy. (C) 1999 Elsevier Science B.V. All rights reserved.