Potential Therapeutic Uses of Thalidomide for Pulmonary Fibrosis

Abstract

Thalidomide was widely used to avoid morning sickness in pregnant women, but was recalled due to its teratogenic effects and malformations in thousands of children. However, potential beneficial effects such as anti-inflammatory, system regulatory activities and the anti-angiogenic effect of thalidomide have been reported. As the studies about thalidomide continued, its new effects and applications made researchers more interested in it and became a promising agent in the treatment of a variety of clinical situations where standard treatments have failed. To make this purpose more achievable, Scopus, Science Direct, Google Scholar, and PubMed were searched. After obtaining and reviewing articles related to thalidomide and its indications, different therapeutic uses of thalidomide for pulmonary diseases are classified on mechanisms. In recent years, thalidomide has been an effective agent in treating cough associated with pulmonary fibrosis and the main suggested mechanism refers to regulation production of inflammatory mediators, including cytokines and chemokines, which trigger Epithelial-Mesenchymal Transition (EMT). The mechanism of EMT is related to the inhibition of Transforming growth factor-beta (TGF-β1)-mediated signaling pathways, Smad2 (Suppressor of Mothers against decapentaplegic homolog 2) / 3, Akt / Glycogen synthase kinase 3 beta (GSK-3β), and Mitogen-activated protein kinase (MAPK). Thalidomide is also involved in paraquat-induced and bleomycin-induced pulmonary fibrosis. Also, Thalidomide gained attention as a suitable agent for the treatment of cough associated with idiopathic pulmonary fibrosis (IPF) and for severe pulmonary damage cause by severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2), responsible for the global pandemic in 2020, due to its anti-inflammatory-anti-angiogenesis and pro-apoptotic properties.