Thymulin inhibits monocrotaline-induced pulmonary hypertension modulating interleukin-6 expression and suppressing p38 pathway

• Autor(a) principal: Henriques-Coelho, Tiago
• Data de Publicação: 2008
• Outros Autores: Oliveira, Sílvia Marta, Moura, Rute S., Roncon-Albuquerque, Roberto, Neves, Ana Luísa, Santos, Mário, Silva, Cristina Isabel Nogueira, La Fuente Carvalho, Filipe, Brandão-Nogueira, Ana, Correia-Pinto, Jorge, Leite-Moreira, Adelino F.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/1822/61470
• topic: Animals; Cytokines; Down-Regulation; Drug Evaluation, Preclinical; Heart; Hemodynamics; Hypertension, Pulmonary; Inflammation Mediators; Interleukin-6; Lung; MAP Kinase Signaling System; Male; Rats; Rats, Wistar; Thymic Factor, Circulating; p38 Mitogen-Activated Protein Kinases; Monocrotaline; Ciências Médicas::Medicina Básica; Science & Technology

The pathogenesis of pulmonary hypertension (PH) includes an inflammatory response. Thymulin, a zinc-dependent thymic hormone, has important immunobiological effects by inhibiting various proinflammatory cytokines and chemokines. We investigated morphological and hemodynamic effects of thymulin administration in a rat model of monocrotaline (MCT)-induced PH, as well as the pattern of proinflammatory cytokine gene expression and the intracellular pathways involved. Adult Wistar rats received an injection of MCT (60 mg/kg, sc) or an equal volume of saline. One day after, the animals randomly received during 3 wk an injection of saline, vehicle (zinc plus carboxymethyl cellulose), or thymulin (100 ng/kg, sc, daily). At d 23-25, the animals were anesthetized for hemodynamic recordings, whereas heart and lungs were collected for morphometric and molecular analysis. Thymulin prevented morphological, hemodynamic, and inflammatory cardiopulmonary profile characteristic of MCT-induced PH, whereas part of these effects were also observed in MCT-treated animals injected with the thymulin's vehicle containing zinc. The pulmonary thymulin effect was likely mediated through suppression of p38 pathway.