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

Abstract

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.