Endothelin-1 as a mediator and potential biomarker for interferon induced pulmonary toxicity.
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.
Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College, London, UK.
Peter M
PM
George
Morven E
ME
Cunningham
Neil
N
Galloway-Phillipps
Rekha
R
Badiger
William
W
Alazawi
Graham R
GR
Foster
Jane A
JA
Mitchell
Hepatitis C; TNFα; biomarker; endothelin-1; innate immunity; interferon; pulmonary hypertension