Idiopathic pulmonary fibrosis (IPF) is definitely a severe progressive fibrotic disease of the lung of unfamiliar etiology that affects approximately 150 0 patients in the United States. the default therapy for IPF was a combination of prednisone N-acetylcysteine and azathioprine but recent trials have shown that this regimen actually raises mortality. An enormous body of work in recent years spanning the bench to the bedside offers radically modified our understanding of Cilostazol the molecular mechanisms underlying IPF. Newer modalities particularly those including monoclonal antibodies targeted at specific pathways known to contribute Cilostazol to the fibrotic process have generated a great deal of exhilaration in the field and recent clinical tests on therapies such as pirfenidone and nintedanib herald a new era in targeted IPF therapies. and studies (23). Initial medical trials showed a tendency toward decreased mortality (24) but the INSPIRE study a larger prospective trial failed to show any survival benefit with subcutaneous IFN-γ treatment (11). In 2012 Cilostazol a small medical trial performed to evaluate the security of inhaled IFN-γ found that individuals in the treatment group showed a reversal in the slope of decrease of their TLC and DLCO (25). FVC and 6MWT showed minimal change. Larger studies are needed to better determine the potential good thing about this therapy. Endothelin Receptor Antagonists Experimental work in the early 1990s shown that Endothelin-1 (ET-1) manifestation is definitely upregulated in IPF (26). It is thought to contribute to neovascularization (27) collagen synthesis (28) and fibroblast proliferation (29) (30). The endothelin receptor antagonist bosentan was found to attenuate bleomycin-induced fibrosis in animal models (31). However no significant difference between the bosentan and placebo arms in the primary end point of six minute walk range (6MWD) was seen in individuals with IPF without evidence of severe Cilostazol pulmonary hypertension (32). More recent data in individuals with IPF found no improvement in main endpoint (progression-free survival) when compared to placebo (33). Two Rabbit Polyclonal to GFR alpha-1. additional endothelin receptor antagonists ambrisentan and macitentan were evaluated in ARTEMIS-IPF and MUSIC respectively. ARTEMIS-IPF a phase III trial was halted due to a lack of efficacy. In addition individuals on the study drug shown more progression and hospitalization than individuals on placebo. MUSIC a phase II trial did not meet its main endpoint of improvement in FVC and there look like no plans for further trials. Sildenafil A substantial proportion of individuals with IPF have been shown to develop pulmonary hypertension over time (34). Sildenafil an oral phosphodiesterase-5 inhibitor is used in the treatment of pulmonary arterial hypertension. Its energy in IPF is definitely unclear but individuals with IPF and concomitant pulmonary hypertension are known to have an increased mortality rate (35). Studies evaluating the use of sildenafil with this establishing offers been shown to improve pulmonary hemodynamics by obstructing PDE-5 in well-ventilated areas of the lung with minimal increase in shunting (36) (37) but a subsequent randomized controlled trial did not meet its main endpoint of 20% improvement in 6MWD at 12 weeks. Additional metrics including dyspnea oxygen pressure and DLCO all showed statistically significant improvements (38). In addition it is important to note that the study did not analyze the subset of individuals who have pulmonary hypertension due to IPF and it is unclear if those individuals would indeed benefit from the drug. Tyrosine Kinase and Serine-Threonine Kinase Inhibitors Numerous protein kinase inhibitors have been developed for the treatment of malignancies through targeted action against particular cells. Protein kinases have been linked to the process of fibrogenesis through the action of growth factors such as TGF-β (39). Tyrosine kinase inhibitors (TKIs) have been used in the treatment of IPF to specifically inhibit the action of fibroblasts effector cells integral to the progression of IPF. Platelet derived growth element (PDGF) offers been shown to induce procollagen production by fibroblasts (40). Imatinib mesylate a tyrosine kinase inhibitor that functions on PDGF Bcr-Abl and c-kit failed to show any improvement in lung function or progression free survival (41). BIBF1120 (right now known as nintedanib) on the other hand acts within the vascular endothelial growth element (VEGF) receptor the fibroblast growth factor.