tetrathiomolybdate and pirfenidone

Idiopathic pulmonary fibrosis is the most common form of the interstitial lung diseases and is characterized by chronic progressive pulmonary parenchymal fibrosis. Although the diagnosis and pathophysiology of this disease have been better characterized over the past few years, there remains no effective therapy for this disease. Therapies initially aimed at inflammation have proven ineffective, and newer strategies targeting aspects of aberrant wound repair involving alveolar epithelial cells or septal endothelial cells are now being investigated. Therapeutic strategies include the anti-fibrotic agents pirfenidone and interferon-gamma. Agents targeting specific cytokines, including connective tissue growth factor, transforming growth factor-beta and chemokines, are being evaluated. The restoration of oxidant balance and inhibition of leukotrienes represent other strategies. Additionally, the role of the coagulation/fibrinolytic systems and angiogenesis has also been examined.

Topics: Angiogenesis Inhibitors; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Antioxidants; Connective Tissue Growth Factor; Humans; Immediate-Early Proteins; Intercellular Signaling Peptides and Proteins; Lung; Molybdenum; Neovascularization, Pathologic; Pulmonary Fibrosis; Pyridones; Randomized Controlled Trials as Topic

Idiopathic pulmonary fibrosis (IPF) is a progressive, fibrosing disease of the distal air spaces of the lung of unknown aetiology. IPF is usually fatal with a median survival of < 3 years. There are currently no effective pharmacotherapeutic agents for the treatment of IPF. In this review, unifying concepts on the pathogenesis of IPF based on understanding of host responses to tissue injury are presented. These host responses involve tightly regulated and contextually orchestrated inflammatory and repair processes. Dysregulation of either of these processes can lead to pathological outcomes. Fibrosis results from an exaggerated or dysregulated repair process that proceeds 'uncontrolled' even after inflammatory responses have subsided. Disease heterogeneity may arise when inflammation and repair are in different (dys)regulatory phases, thus accounting for regional disparity. Usual interstitial pneumonia (UIP), the histopathological correlate of clinical IPF, represents a more fibrotic tissue reaction pattern and for which anti-inflammatory agents are ineffective. Emerging 'antifibrotic' drugs and strategies for UIP/IPF are discussed. The importance of accurately phenotyping a highly heterogeneous disease process that may require individualised and 'combined' therapies is emphasised.

Topics: Acetylcysteine; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Connective Tissue Growth Factor; Eicosanoids; Endothelin-1; Humans; Immediate-Early Proteins; Intercellular Signaling Peptides and Proteins; Interferon-gamma; Molybdenum; Protein Kinase Inhibitors; Proteins; Pulmonary Fibrosis; Pyridones; Recombinant Proteins; Relaxin; Renin-Angiotensin System; Tumor Necrosis Factor-alpha