Prolonged treatment with recombinant interferon gamma induces erythema nodosum leprosum in lepromatous leprosy patients.

10 patients with borderline and lepromatous leprosy were selected for a prolonged trial with recombinant interferon gamma (rIFN-gamma). Patients received 30 micrograms intradermally for six injections over a 9-d period, and then either 100 micrograms intradermally every 1 mo for 10 mo or every 2 wk for 5 mo (total, 1.2 mg). Erythema nodosum leprosum (ENL) was induced in 60% of the patients within 6-7 mo, as compared with an incidence of 15% per year with multiple drug therapy alone. The mean whole-body reduction in bacterial index over the first 6 mo was 0.9 log units. Cutaneous induration at the intradermal injection sites of greater than or equal to 15 mm predicted the development of a subsequent reactional state. Monocytes obtained from patients receiving the lymphokine demonstrated an increased respiratory burst and a 2.5-5.1-fold increase in tumor necrosis factor alpha (TNF-alpha) secretion in response to agonists. Patients in ENL had an even higher release of TNF-alpha from monocytes as well as high levels of TNF-alpha in the plasma (mean, 2,000 pg/ml). Thalidomide therapy was required to treat the systemic manifestations of ENL. Control of toxic symptoms with thalidomide was associated with a 50-80% reduction in agonist-stimulated monocyte TNF-alpha secretion. IFN-gamma enhanced the monocyte release of TNF-alpha by 3-7.5-fold (agonist dependent) when added to patient's cells in vitro, and this could be suppressed by the in vitro addition of 10 micrograms/ml of thalidomide.

Effect of rhuIFN-gamma treatment in multibacillary leprosy patients.

Previous studies have shown that when multibacillary leprosy patients were treated with recombinant human interferon gamma (rhuIFN-gamma) for 6-10 months there was an accelerated reduction in the number of acid-fast bacilli in the skin at the site of injection as well as an accelerated bacillary reduction at distal sites. However, this favorable out-come of IFN-gamma treatment was associated with the development of erythema nodosum leprosum (ENL). The present study was undertaken to investigate whether rhuIFN-gamma-induced bacillary clearance could be disassociated from the induction of ENL. rhuIFN-gamma was administered together with thalidomide and conventional multidrug chemotherapy to newly diagnosed leprosy patients. During treatment with this combination of drugs, the mean reduction in bacterial load was the same as the reduction observed with chemotherapy alone. Moreover, the inclusion of thalidomide in the treatment regimen was associated with a low frequency of ENL episodes. A second group of leprosy patients, who had already completed 2 years of chemotherapy, were treated with rhuIFN-gamma only. In those patients who were skin bacilli negative, ENL did not occur during rhuIFN-gamma treatment. In contrast, in bacilli-positive patients the frequency of ENL during rhuIFN-gamma treatment was higher, as was the occurrence of local erythema and induration. However, rhuIFN-gamma treatment without concomitant chemotherapy did not result in a reduction in the bacterial load in the skin of bacilli-positive patients. These findings, taken together, indicate that rhuIFN-gamma does not, by itself, accelerate bacterial clearance, but requires concomitant chemotherapy to achieve the accelerated reduction in bacillary load. Thalidomide reduces the frequency of IFN-gamma-induced ENL, but also eliminates the IFN-gamma-induced bacillary clearance.

Imunidade celular e humoral na hanseníase bordeline tuberculoid (BT) / Humoral and cellular immunity in bordeline tuberculoid (BT) leprosy

Foram estudados 20 pacientes com diagnóstico de hanseníase bordeline tuberculoid (BT), classificados segundo os critérios de Ridley & Jopling, bem como dois pacientes com forma Tuberculoid tuberculoid (TT), todos com baciloscopia negativa, exceto um, que apresentou índice baciloscópico 1+. Todos os pacientes foram avaliados quanto a sua capacidade de resposta imune humoral ao DBSA (antígeno sintético semelhante ao glicolipídeo fenólico I, específico do M, leprae) e 18 pacientes foram submetidos a testes de avaliaçåo da resposta imunocelular in vivo (teste Mitsuda) e in vitro (linfoproliferaçåo e produçåo de interferon-gama) frente ao Mycobacterium leprae. Observamos que 90 por cento dos pacientess apresentaram resultados negativos quanto à pesquisa de IgM anti-DBSA pelo método imunoenzimático ELISA (densidade óptica , 0,27), o que demonstra ser este teste inadequado para a detecçåo de pacientes paucibacilares. Quanto aos testes de imunidade celular, oito pacientes (44,4 por cento) apresentaram teste de Mitsuda positivo (>= 5mm), sendo os demais considerados negativos. Cerca de 89 por cento dos pacientes tiveram teste de Mitsuda maior ou igual a 3mm. Doze pacientes (66,7 por cento) tiveram resposta linfoproliferativa positiva (índice estimulatório >= 3,0) para o M. leprae. Vinte e dois por cento dos pacientes apresentaram níveis de interferon-gama acima do limite de positividade (40 U/ml). Houve 66,7 por cento de correlaçåo entre os testes de Mitsuda e interferon-gama; 55,6 por cento de correlaçåo entre os testes in vitro (linfoproliferaçåo e interferon-gama). Quando estes três testes foram considerados em conjunto, uma correlaçåo de 38,9 por cento foi observada. Este estudo demonstra a heterogeneidade do comportamento imunológico mediado por células e anticorpos em pacientes com hanseníase BT, apesar de todos histologicamente serem capazes de conter a multiplicaçåo bacilar e de formar granulomas epitelióides