A Silica-Induced Pulmonary Fibrosis Model: Are We Closer to ‘Real Life’

It is important to emphasize that the bleomycin model, the most ubiquitous experimental model of lung fibrosis, is a paradigm of the inflammatory route. Findings in animals sacrificed at early stages (i.e. 3 days postinstillation) are almost exclusively inflammatory, while those sacrificed at later stages (i.e. 14–21 days postinstillation) show both inflammation and fibrosis. Thus, the bleomycin model is useful for investigating the fibrotic response to acute lung injury and for evaluating the short-term treatment with various drugs, but not for mimicking human IPF [4] . In this issue of International Archives of Allergy and Immunology , Shimbori et al. [5] presented a very wellconducted study on silica-induced pulmonary fibrosis, and showed that treatment with a highly selective CysLT1 receptor antagonist (pranlukast) has antifibrotic effects that are independent of any effect on the acute inflammatory response. One of the most important findings of the present study is that long-term treatment (10 weeks) with pranlukast significantly attenuated the development of pulmonary fibrosis, while short-term treatment (2 weeks) failed to inhibit the initial increase in hydroxyproline content in the fibrotic lungs. These results demonstrate that the beneficial antifibrotic effect of the long-term pranlukast treatment regimen may be due to the inhibition of the progression of fibrosis rather than the inhibition of the onset of fibrosis. In addition, the number of inflamIdiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease that is associated with high mortality rates and is unresponsive to currently available treatments. The study of IPF in humans is complicated by the fact that its natural history is unknown and the evolution of the process is unclear. By the time patients seek medical treatment for symptoms the disease process is generally advanced [1] . A growing body of evidence suggests that, unlike other interstitial lung diseases, IPF is a distinct entity in which inflammation is a secondary and nonrelevant pathogenic partner. It has been suggested that IPF is characterized by a sequence of events that starts with alveolar epithelial microinjuries followed by the formation of fibroblastic foci and resulting in an exaggerated deposition of the extracellular matrix, which drives the destruction of the lung parenchyma architecture [2, 3] . Animal models have been developed to study the evolution of fibrotic responses and these have identified a number of key cells, mediators and processes that are likely involved in human IPF. However, no current animal model is capable of recapitulating all of these cardinal manifestations of the human disease. As such, there are no appropriate experimental models of IPF, not only because we do not know its etiology, but also because all the traditional models start with an inflammatory reaction in spite of the fact that IPF is now accepted as being a noninflammatory disease. Published online: March 1, 2012