Assuntos
Cicatrização , Cricetinae , Células CHO , Células de Langerhans , Células de Langerhans/fisiologia , Células de Langerhans/patologia , Escherichia coli/genética , Fator Estimulador de Colônias de Granulócitos , Fatores de Tempo , Hanseníase Dimorfa/fisiopatologia , Hanseníase Dimorfa/patologia , Hanseníase Dimorfa/tratamento farmacológico , Hanseníase Virchowiana/fisiopatologia , Hanseníase Virchowiana/patologia , Hanseníase Virchowiana/tratamento farmacológico , Injeções Intradérmicas , Injeções Subcutâneas , Leucócitos , Leucócitos/fisiologia , Macrófagos , Microscopia Eletrônica , Pele , Pele/fisiopatologia , Pele/patologia , Pele/ultraestrutura , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Queratinócitos , Queratinócitos/fisiologia , Queratinócitos/patologiaAssuntos
Adolescente , Anticorpos Antibacterianos/análise , Antígenos de Bactérias/análise , Contagem de Leucócitos , Fatores de Tempo , Hanseníase Virchowiana/terapia , Imunidade Celular , /administração & dosagem , Microscopia Eletrônica , Mycobacterium leprae/imunologia , Proteínas Recombinantes/uso terapêutico , Relação Dose-Resposta a DrogaRESUMO
The local response to single intradermal injection of 10 ug recombinat gamma-interferon (rIFNgamma) has been studied in 17 patients with lepromatous leprosy. Of these, 2 patients additionally received two intradermal injections of 10 ug rIFNgamma at received another site. The results were compared with those of 3 patients who received three injections of the same dose at a single site in an earlier study. One to 7 days after lymphokine administration 4-mm pinch biopsies were obtained and axamined for cellular alterations in the dermis and epidermis. This allowed a kinetic analysis of mononuclear cell infiltration, keratinocyte proliferation and differentiation and Langerhans cell redistribution. At 24 hours, the migration of large numbers of helper T cells and monocytes was already prominent and associated with induration. Mononuclear cell eccumulation peaked at 72 hours but then persisted for 5-7 days. Only smal numbers (one-third or less of toal T cells) of suppressor/cytotoxic T cells were present at any time, and granulocytes were absent. Two daily injections of rIFNgamma led to a more intense accumulation of cells. Ten ug of rIFNgamma resulted in enhanced keratinocyte proliferation, Ia expression, and thickening of the epidermis. At 24-48 hours major histocompatibility Class II (Ia) antigen was first noted on the dividing cells of the basal layer. By 72-96 hours the entire epidemir exhibited strong expression of Ia antigen on cell surfaces. Repeated doses of lymphokine accentuated these changes and resulted in a more prompt keratinization and sloughing of this layer. Whereas a single dose of rIFNgamma resulted in the upward movement of T6+ Langerhans cells (LCs) in the epidermis, two injections led to a 50% reduction in their numbers and three doses were associated with an almost total loss of detectable T6+ LCs from the epidermis. These are probably aloughed along with keratinocytes. In contrast to the situation with a delayed immune response in the skin (purified protein derivative), no LCs accumulated in the dermis in association with helper T cells