Thalidomide interaction with inflammation in idiopathic pulmonary fibrosis

Abstract

The “Thalidomide tragedy” is a landmark in the history of the pharmaceutical industry. Despite limited clinical trials, there is a continuous effort to investigate thalidomide as a drug for cancer and inflammatory diseases such as rheumatoid arthritis, lepromatous leprosy, and COVID-19. This review focuses on the possibilities of targeting inflammation by repurposing thalidomide for the treatment of idiopathic pulmonary fibrosis (IPF). Articles were searched from the Scopus database, sorted, and selected articles were reviewed. The content includes the proven mechanisms of action of thalidomide relevant to IPF. Inflammation, oxidative stress, and epigenetic mechanisms are major pathogenic factors in IPF. Transforming growth factor-β (TGF-β) is the major biomarker of IPF. Thalidomide is an effective anti-inflammatory drug in inhibiting TGF-β, interleukins (IL-6 and IL-1β), and tumour necrosis factor-α (TNF-α). Thalidomide binds cereblon, a process that is involved in the proposed mechanism in specific cancers such as breast cancer, colon cancer, multiple myeloma, and lung cancer. Cereblon is involved in activating AMP-activated protein kinase (AMPK)-TGF-β/Smad signalling, thereby attenuating fibrosis. The past few years have witnessed an improvement in the identification of biomarkers and diagnostic technologies in respiratory diseases, partly because of the COVID-19 pandemic. Hence, investment in clinical trials with a systematic plan can help repurpose thalidomide for pulmonary fibrosis. Graphical Abstract

Network pharmacology and in silico approaches to uncover multitargeted mechanism of action of Zingiber zerumbet rhizomes for the treatment of idiopathic pulmonary fibrosis

“…83 As a result of a lung injury followed by an EMT brought on by TGF-β1 and differentiates myofibroblast with the growth factor receptors activation to increase the ECM deposition. 84,85 Chinese traditional medicines are considered over Western medicines, and many of them have been clinically shown effective in treating several diseases with a patent approach, and when treating the condition, these drugs interact with multiple pathways and targets. 86 In traditional medicine practices, a wide range of diseases was treated using natural products such as Chinese and Indian traditional medicine.…”

Identification of shared hub genes in lung cancer and rheumatoid arthritis patients using bioinformatics approaches

“…Additionally, it enhances the attack of the immune system on cancer cells, suppressing immune evasion in lung cancer [25]. In the treatment of RA, it modulates immune responses and reduces the release of inflammatory mediators, effectively alleviating joint pain and swelling in patients [26]. Despite the potential efficacy of these drugs in treating lung cancer and RA, their toxicity limits their application.…”

Screening for central targets and the commonalities between rheumatoid arthritis and idiopathic pulmonary fibrosis based on bioinformatics

“…IPF is the predominant form of ILD. It is characterized by chronic brotic scarring of lung tissue leading to progressive deterioration of respiratory function and eventual death [9,10]. Clinical reports indicate that patients with RA and IPF share some similarities in the development of the disease and in the clinical features, but the mechanisms involved have not yet been clearly understood [3,4,11].…”

“…Furthermore, chronic in ammation not only ampli es conventional risk factors but also facilitates recruitment of immune cells. Although the role of in ammation in IPF pathogenesis remains debatable, approved treatments for IPF exhibit antiin ammatory effects [10,[22][23][24]. And various in ammatory mediators play an important role in driving pulmonary brosis.…”