Interferon-α elevates pulmonary blood pressure in sheep—the role of thromboxane cascade

• Published in: European journal of pharmacology 1999-04, Vol.370 (2), p.145-151
• Main Authors: Hanaoka, Masayuki, Kubo, Keishi, Hayano, Toshihide, Koizumi, Tomonobu, Kobayashi, Toshio
• Format: Article
• Language: English
• Subjects: 6-Ketoprostaglandin F1 alpha - blood; Analysis of Variance; Animals; Antiviral Agents - pharmacology; Body Temperature - drug effects; Capillary Permeability - drug effects; Enzyme Inhibitors - therapeutic use; Hemodynamics - drug effects; Hypertension, Pulmonary - chemically induced; Hypertension, Pulmonary - prevention & control; Infusions, Intravenous; Interferon-alpha - pharmacology; Interferon-α; Lung - drug effects; Lung - physiopathology; Methacrylates - therapeutic use; Permeability; Pulmonary hypertension; Sheep; Thromboxane A 2; Thromboxane B2 - blood; Thromboxane B2 - metabolism; Thromboxane-A Synthase - antagonists & inhibitors
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(99)00107-7

We tested the effect of interferon-α on lung function to examine whether interferon-α causes some pathophysiological change in the lung. We prepared awake sheep with chronic lung lymph fistula, and measured the pulmonary hemodynamics, lung fluid balance and concentrations of prostanoid products. At 1 h after intravenous interferon-α administration (18×10 6 I.U.), pulmonary arterial pressure and pulmonary vascular resistance were significantly increased compared to the baseline values. The levels of thromboxane B 2 in both plasma and lung lymph were increased concomitant with early elevation on pulmonary arterial pressure. In addition, OKY-046 {sodium-3-[4-(1-imidazolylmethyl)phenyl]-2-propenoic acid} (10 mg kg −1), a selective thromboxane synthase inhibitor, significantly prevented the interferon-α-induced pulmonary hypertension and thromboxane B 2 production. While no evidence of increased pulmonary vascular leakage was observed. These findings suggest that a single infusion of interferon-α stimulates a thromboxane cascade and causes transient pulmonary hypertension. However, interferon-α itself or increased thromboxane A 2 might not affect the pulmonary vascular permeability in sheep.