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

We tested the effect of interferon-alpha on lung function to examine whethe r interferon-alpha causes some pathophysiological change in the lung. We pr epared awake sheep with chronic lung lymph fistula, and measured the pulmon ary hemodynamics, lung fluid balance and concentrations of prostanoid produ cts. At 1 h after intravenous interferon-alpha administration (18 x 10(6) I .U.), pulmonary arterial pressure and pulmonary vascular resistance were si gnificantly increased compared to the baseline values. The levels of thromb oxane B-2 in both plasma and lung lymph were increased concomitant with ear ly elevation on pulmonary arterial pressure. In addition, OKY-046 {sodium-3 -[4-(1-imidazolylmethyl)phenyl]-2-propenoic acid} (10 mg kg(-1)), a selecti ve thromboxane synthase inhibitor, significantly prevented the interferon-a lpha-induced pulmonary hypertension and thromboxane B2 production. While no evidence of increased pulmonary vascular leakage was observed. These findi ngs suggest that a single infusion of interferon-alpha stimulates a thrombo xane cascade and causes transient pulmonary hypertension. However, interfer on-a itself or increased thromboxane A(2) might not affect the pulmonary va scular permeability in sheep. (C) 1999 Elsevier Science B.V. All rights res erved.