RESUMO
The current study determined if interleukin-6 (IL-6) had a causative role in the lung dysfunction and/or surfactant alterations associated with three different lung insults. IL-6 (or saline) was instilled into rats followed by mechanical ventilation in vivo for 4 hours. Also, IL-6 (-/-) and wild-type mice were subjected to 3 insults: ex vivo injurious mechanical ventilation; cecal ligation and perforation; and hyperoxia exposure. In all experiments, the presence or absence of IL-6 did not significantly influence gas exchange, lung compliance, or various surfactant measurements. These results suggest that IL-6 may have a limited role in the surfactant alterations observed in acute lung injury.
Assuntos
Interleucina-6/imunologia , Interleucina-6/farmacologia , Pulmão/efeitos dos fármacos , Surfactantes Pulmonares/metabolismo , Síndrome do Desconforto Respiratório/imunologia , Animais , Lavagem Broncoalveolar/efeitos adversos , Ceco/lesões , Modelos Animais de Doenças , Hiperóxia/complicações , Interleucina-6/genética , Pulmão/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos , Camundongos Transgênicos , Ratos , Ratos Sprague-Dawley , Respiração Artificial/efeitos adversos , Síndrome do Desconforto Respiratório/etiologia , Sepse/tratamento farmacológico , Sepse/imunologiaRESUMO
Matrix metalloproteinases (MMPs) are degradative enzymes, which act to remodel tissue. Their activity is regulated by the tissue inhibitors of metalloproteinases (TIMPs). An imbalance in the degradation/inhibition activities has been associated with many diseases, including sepsis. We have previously shown that TIMP-3 knockout animals develop spontaneous, progressive air space enlargement. The objectives of this study were to determine the effects of a septic lung stress induced by cecal ligation and perforation (CLP) on lung function, structure, pulmonary surfactant, and inflammation in TIMP-3 null mice. Knockout and wild-type animals were randomized to either sham or CLP surgery, allowed to recover for 6 h, and then euthanized. TIMP-3 null animals exposed to sham surgery had a significant increase in lung compliance when compared with sham wild-type mice. Additionally, the TIMP-3 knockout mice showed a significant increase in compliance following CLP. Rapid compliance changes were accompanied by significantly decreased collagen and fibronectin levels and increased gelatinase (MMP-2 and -9) abundance and activation. Additionally, in situ zymography showed increased airway-associated gelatinase activity in the knockout animals enhanced following CLP. In conclusion, exposing TIMP-3 null animals to sepsis rapidly enhances the phenotypic abnormalities of these mice, due to increased MMP activity induced by CLP.