A novel chronic murine model of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a debilitating disease with a difficult treatment that generates high costs to health systems. It causes a progressive reduction to the respiratory function, which leads to often lethal comorbidities. Although there are therapies capable to slow disease9s progress, they do not lead to cure nor are able to ameliorate patient9s life quality. So, the research for new therapies to cure IPF is still in order. To develop new drugs, it9s necessary an animal model of chronic disease with low costs and high reproducibility. Literature shows that the major model is bleomicin (BLM) intratracheally instilated C57bl6 mice. However, these animals develop an acute fibrosis that leans to self-healing, what difficult the analyses of new drugs9 efficacy. Thus, this work aimed to develop an animal model of chronic pulmonary fibrosis using BALB/c mice. They are classified as resistant to pulmonary fibrosis, however when in context of pneumomicosis they do develop fibrosis. Therefore, we hypothesized that pulmonary fibrosis in BALB/c mice could be induced by BLM with a longer time course for the disease in result of a milder but prolonged inflammatory response. We indeed observed the progress of the fibrosis on the histopathological analysis, with inflammation after 5 days followed by collagen deposits and a well-established fibrosis after 15 and 30 days, respectively. The ventilatory mechanics were consistent with the histological findings, with progressive decay of respiratory function. Furthermore, the mRNA accumulation and the cytokine profile are consistent with fibrosis profile. Combined, this data indicate that BALB/c mice can be used as a chronic pulmonary fibrosis experimental model.