03183nas a2200445   4500000000100000008004100001260001600042653001500058653001000073653002600083653001000109653001600119653001200135653003000147653001100177653001100188653002100199653002300220653001200243653002600255653000900281653001600290653001400306653002500320653001300345653000900358100001900367700001300386700001300399700001400412700002000426700001700446700001300463700001300476245009500489300001200584490000700596520212000603022001402723       1999                            d  c1999 Mar 1510aAdolescent10aAdult10aAntibodies, Bacterial10aChild10aClofazimine10aDapsone10aDrug Therapy, Combination10aFemale10aHumans10aInterferon-gamma10aLeprostatic Agents10aleprosy10aLymphocyte Activation10aMale10aMiddle Aged10aNeopterin10aRecombinant Proteins10aRifampin10aSkin1 aBarral-Netto M1 aSantos S1 aSantos I1 aSohsten R1 aBittencourt A L1 aCarvalho E M1 aBarral A1 aWaters M00aImmunochemotherapy with interferon-gamma and multidrug therapy for multibacillary leprosy.  a185-2010 v723 a<p>Treatment for multibacillary leprosy is presently performed with a multidrug therapy (MDT) scheme maintained for 2 years. Leprosy treatment however can benefit from the reduction of length. The lack of interferon-gamma (IFN-gamma) 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 clinical 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/m2 followed by 10 daily doses of 10(7) IU IFN-gamma/m2, intramuscularly, during the first 20 days of MDT. IFN-gamma was well tolerated and did not cause any increase in the rate of leprosy reactions development during treatment. Decrease of bacillary load, fall of anti-Mycobacterium leprae IgG serum antibodies, changes of histological pattern, as well as changes in lymphocyte proliferation assay in response to mitogens (PHA or PWM), M. leprae antigen or PPD was similar in both groups of patients. Among several soluble immunological markers measured before and 30 days after beginning of treatment, levels of soluble IL-2R receptor 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. Soluble CD4 and soluble CD8 markers did not change significantly in either group of patients. Neopterin, a marker of macrophage activation, increased in all but one patient treated with MDT + IFN-gamma but in none treated with MDT alone, indicating that IFN-gamma was active in vivo. Our findings indicate that despite being able to promote macrophage activation in multibacillary 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.</p>  a0001-706X