Eltrombopag inhibits Type I interferon-mediated antiviral signaling by decreasing cellular iron

  • Biochem Pharmacol. 2021 Apr;186:114436. doi: 10.1016/j.bcp.2021.114436.
Sai Ma  1 ,  Anli Liu  1 ,  Xiang Hu  2 ,  Qi Feng  1 ,  Yanqi Zhang  3 ,  Nailin Li  4 ,  Jun Peng  5 ,  Zi Sheng  6
Affiliations
  • 1. Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 2. Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China; Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Jinan, China.
  • 3. Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 4. Department of Medicine-Solna, Clinical Epidemiology Unit, Clinical Pharmacology Group, Karolinska Institute, Stockholm, Sweden.
  • 5. Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China; State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. Electronic address: [email protected].
  • 6. Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China; School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China. Electronic address: [email protected].
PMID: 33539815 DOI: 10.1016/j.bcp.2021.114436
Abstract

Thrombocytopenia is common among patients with viral hepatitis, limiting the use of Antiviral therapy. Eltrombopag (EP) is a Thrombopoietin Receptor (TPO-R) agonist that has been approved for treatment of immune thrombocytopenia patients with hepatitis virus Infection. Interferon-α (IFN-α) plays a crucial role in the Antiviral response, and is recommended as the first-line agent for chronic hepatitis B patients. Here, we investigated whether EP inhibits the production of IFN-stimulated genes (ISGs) induced by IFN-α through the TPO-R-independent pathway by mediating Reactive Oxygen Species production by iron chelation. Our results assessed the inhibitory effect of EP on IFN-α signaling, which contributes to the downregulation of ISGs produced by monocytes and sheds light on the underlying mechanisms using iron chelation to treat patients with hepatitis-related immunological thrombocytopenia.

Keywords
Eltrombopag; IFN-stimulated gene; Interferon-α; Iron chelation; Reactive oxygen species; Thrombocytopenia; Viral hepatitis.
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