RESUMO
Cutaneous leishmaniasis (CL) is the most common clinical form of American tegumentary leishmaniasis caused by Leishmania (Viannia) braziliensis. CL is associated with a strong Th1 immune response. This exacerbated inflammatory response is correlated with severity of disease and delays the healing time of the ulcer. The fourth-generation immucillin derivative (DI4G), a potent inhibitor of purine nucleoside phosphorylase, has been proposed as a promising agent in the treatment of diseases associated with T cell activation. Herein, we evaluated the in vitro immunomodulatory activity of DI4G in cells of patients presenting with CL. Peripheral blood mononuclear cells (PBMC) from CL patients were stimulated with soluble leishmania antigen (SLA), in the presence or absence of DI4G, and IFN-γ, TNF, CXCL9, and CXCL10 levels were determined by ELISA. Lymphocyte proliferation in the presence or absence of DI4G was also evaluated, using flow cytometry. DI4G was able to decrease (p < 0.05) IFN-γ production but did not change the TNF, CXCL9, and CXCL10 levels. DI4G decreased (p < 0.05) the lymphoproliferative response mediated by CD8+ T cells, but not that by CD4+ T cells. DI4G is able to attenuate the exaggerated immune response in CL, exhibiting immunomodulatory activity in IFN-γ production and in CD8+ T cell proliferation.
Assuntos
Adenina/análogos & derivados , Células Matadoras Naturais/imunologia , Leishmania braziliensis/imunologia , Leishmaniose Cutânea/tratamento farmacológico , Leucócitos Mononucleares/imunologia , Purina-Núcleosídeo Fosforilase/antagonistas & inibidores , Pirrolidinas/farmacologia , Células Th1/imunologia , Adenina/química , Adenina/farmacologia , Adenosina/análogos & derivados , Brasil , Proliferação de Células , Células Cultivadas , Citocinas/metabolismo , Humanos , Imunomodulação , Ativação Linfocitária , Pirrolidinas/químicaRESUMO
AbstractCutaneous leishmaniasis (CL) by Leishmania braziliensis is associated with decreasing cure rates in Brazil. Standard treatment with pentavalent antimony (Sbv) cures only 50-60% of the cases. The immunopathogenesis of CL ulcer is associated with high interferon-γ and tumor necrosis factor (TNF) production. Pentoxifylline, a TNF inhibitor, has been successfully used in association with Sbv in mucosal and cutaneous leishmaniasis. This randomized, double-blind, and placebo-controlled trial aimed to evaluate the efficacy and safety of oral pentoxifylline plus Sbv versus placebo plus Sbv in patients with CL in Bahia, Brazil. A total of 164 patients were randomized in two groups to receive the combination or the monotherapy. Cure rate 6 months after treatment was 45% in the pentoxifylline group and 43% in the control group. There was also no difference between the groups regarding the healing time (99.7 ± 66.2 days and 98.1 ± 72.7 days, respectively). Adverse events were more common in the pentoxifylline group (37.8%), versus 23% in the placebo group. This trial shows that Sbv combined therapy with pentoxifylline is not more effective than Sbv monotherapy in the treatment of CL caused by L. braziliensis.
Assuntos
Antimônio/uso terapêutico , Antiprotozoários/uso terapêutico , Leishmania braziliensis/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Pentoxifilina/uso terapêutico , Adolescente , Adulto , Brasil , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Interferon gama/antagonistas & inibidores , Interferon gama/biossíntese , Interferon gama/imunologia , Leishmania braziliensis/crescimento & desenvolvimento , Leishmania braziliensis/patogenicidade , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/parasitologia , Leishmaniose Cutânea/patologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Urinary symptoms occur in 19% of human T-cell lymphotropic virus type 1 (HTLV-1)-infected patients who do not fulfill criteria for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and in almost 100% of HAM/TSP patients. Few studies have evaluated therapies for overactive bladder (OAB) caused by HTLV-1 infection. This case report describes the effect of onabotulinum toxin A on the urinary manifestations of three patients with HAM/TSP and OAB symptoms. The patients were intravesically administered 200 units of Botox®. Their incontinence episodes improved, and their OAB symptoms scores (OABSS) reduced significantly. These data indicate that Botox® should be a treatment option for OAB associated with HTLV-1 infection.