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Interferon-beta
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Interleukin-1
Interleukin-6 receptor
Transforming growth factor-beta (TGF-beta)
Tumor necrosis factor-alpha (TNF-alpha)
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This patient presents with a chronic dry cough, exertional dyspnea, bibasilar lung crackles, and a restrictive pattern on PFTs (FEV1/FVC >70%), indicative of idiopathic pulmonary fibrosis (IPF). TGF-beta is one of the pro-fibrotic cytokines that are targeted by IPF treatments. IPF is characterized by gradual-onset exertional dyspnea, nonproductive cough, bibasilar lung crackles, and/or clubbing, and generally presents in patients over 60 years of age with a smoking history. IPF is thought to result from unregulated cycles of epithelial cell damage and repair in response to an initial insult, and is marked by fibroblastic proliferation. This is promoted by pro-fibrotic cytokines including TGF-beta (which increases connective tissue synthesis), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF). Medical treatment for IPF can consist of agents that inhibit the action of these factors. Nintedanib inhibits the tyrosine kinases that serve as receptors for FGF, VEGF, and PDGF. Similarly, pirfenidone is an inhibitor of TGF-beta. King Jr et al. review the pathogenesis and treatment of IPF. They highlight the central role of epithelial cell injury and fibroblastic proliferation in pathogenesis. Incorrect Answers: Answer 1: Interferon-beta is a disease-modifying therapy for multiple sclerosis, which presents with focal neurological findings disseminated in space and time (e.g., optic neuritis, focal weakness). Interferon-beta is an immunomodulator that decreases inflammation; however, it is not used in the treatment of IPF. Answer 2: Interleukin-1 is a cytokine that plays a role in acute inflammation and fever. It is competitively inhibited by anakinra, which is used in the treatment of rheumatoid arthritis. Rheumatoid arthritis presents with morning joint stiffness, joint pain, and constitutional symptoms (e.g., malaise). Interleukin-1 is not a therapeutic target in IPF. Answer 3: Interleukin-6 receptor is the receptor for a cytokine that is involved in the fever response and generation of acute-phase reactants. It is targeted by tocilizumab in the treatment of rheumatoid arthritis. Interleukin-6 may have a pathogenic role in IPF, but is not a therapeutic target in IPF. Answer 5: Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine that promotes vascular endothelial leakage to recruit leukocytes to sites of infection. Its inhibitors, including etanercept, are used in the treatment of rheumatoid arthritis. It is not a therapeutic target in IPF. Bullet Summary: Transforming growth factor-beta, platelet-derived growth factor, fibroblast growth factor, and vascular endothelial growth factor are targets of idiopathic pulmonary fibrosis treatment.
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