Open AccessEndothelin‐1 as a Mediator and Potential Biomarker for Interferon Induced Pulmonary Toxicity
Author(s) -
George Peter M.,
Cunningham Morven E.,
GallowayPhillipps Neil,
Badiger Rekha,
Alazawi William,
Foster Graham R.,
Mitchell Jane A.
Publication year - 2012
Publication title -
pulmonary circulation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.791
H-Index - 40
ISSN - 2045-8940
DOI - 10.4103/2045-8932.105039
Subject(s) - medicine , mediator , endothelin 1 , endothelin receptor , pulmonary hypertension , interferon , immunology , pharmacology , receptor
Endothelin‐1 is a potent vasoconstrictor and a therapeutic target in pulmonary arterial hypertension. Endothelial cells are the physiological source of endothelin‐1 but in vitro data from our group shows that interferons (IFNα, IFNβ or IFNγ) induce endothelin‐1 in pulmonary vascular smooth muscle cells. IFNs are integral to innate immunity and their antiviral and immunomodulatory capability has been harnessed therapeutically; for example, IFNα plays a critical role in the treatment of chronic hepatitis C infection. However, in some patients, IFN causes pneumonitis and possibly irreversible pulmonary arterial hypertension. In this study, we found that of 16 patients undergoing a six‐month course of IFNα therapy, two demonstrated considerably increased serum levels of endothelin‐1. We propose that IFN therapy results in elevated levels of endothelin‐1 in some patients and when clinically significant levels are reached, pulmonary side effects could ensue. This hypothesis can be easily tested in IFN‐treated patients by measuring serum endothelin‐1 levels and cardiopulmonary physiological parameters.