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

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.