Thalidomide interaction with inflammation in idiopathic pulmonary fibrosis

Area of Science:

• Pharmacology
• Pulmonology
• Immunology

Background:

• Thalidomide, despite its controversial past, is being re-investigated for various inflammatory conditions.
• Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by inflammation, oxidative stress, and epigenetic alterations.
• Transforming growth factor-beta (TGF-β) is a critical biomarker in IPF pathogenesis.

Purpose of the Study:

• To review the potential of repurposing thalidomide for treating idiopathic pulmonary fibrosis (IPF).
• To explore thalidomide's mechanisms of action relevant to IPF's inflammatory and fibrotic processes.

Main Methods:

• Literature search conducted on the Scopus database.
• Articles were sorted and selected for review based on relevance to thalidomide and IPF.
• Analysis of thalidomide's anti-inflammatory and anti-fibrotic mechanisms, including its interaction with cereblon and signaling pathways.

Main Results:

• Thalidomide demonstrates potent anti-inflammatory effects by inhibiting TGF-β, IL-6, IL-1β, and TNF-α.
• Thalidomide's binding to cereblon activates AMPK-TGF-β/Smad signaling, which is crucial for attenuating fibrosis.
• Evidence suggests thalidomide's mechanisms are relevant to mitigating IPF pathology.

Conclusions:

• Thalidomide's established anti-inflammatory and anti-fibrotic properties make it a viable candidate for IPF treatment.
• Further investment in well-designed clinical trials is recommended to validate thalidomide repurposing for pulmonary fibrosis.
• Advancements in biomarker identification and diagnostics, accelerated by the COVID-19 pandemic, can support such clinical investigations.