Interleukin-2-induced lung injury is mediated by oxygen free radicals

J. M. Klausner, I. S. Paterson, G. Goldman, L. Kobzik, S. Lelcuk, Y. Skornick, Timothy Eberlein, C. R. Valeri, D. Shepro, H. B. Hechtman

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Abstract

Interleukin-2 therapy leads to respiratory dysfunction caused by increased vascular permeability. This study examines the role of oxygen-derived free radicals (OFR). Sheep (n = 6) with chronic lung lymph fistulae were given interleukin-2, 105 units/kg, as an intravenous bolus. The mean pulmonary artery pressure rose from 13 to 23 mm Hg (p < 0.05) at 1 hour and remained elevated for 4 hours, although the pulmonary artery wedge pressure was unchanged at 4 mm Hg. Arterial oxygen tension fell from 88 to 77 mm Hg (p < 0.05). Lung lymph flow rose from 2.2 to 6.4 ml/30 min (p < 0.05) at 3 hours. This rise coincided with an increase in the lymph/plasma protein ratio from 0.67 to 0.77 (p < 0.05) and lymph protein clearance from 1.5 to 4.4 ml/30 min (p < 0.05), indicating increased lung microvascular permeability. Interleukin-2 led to transient increases in plasma thromboxane B2 from 168 to 388 pg/ml (p < 0.05) and lung lymph thromboxane B2 from 235 to 694 pg/ml (p < 0.05). The leukocyte count fell from 8156 to 4375/mm3 (p < 0.05) primarily caused by a 78% drop in lymphocyte count. Platelet count declined from 292 to 184 X 103/mm3 (p < 0.05). Pretreatment with the hydroxyl radical scavenger dimethylthiourea, 1 gm/kg, intravenously, (n = 6) prevented the interleukin-2-induced increase in mean pulmonary artery pressure, lung lymph flow, lymph/plasma protein ratio, lymph protein clearance, and thromboxane B2 levels in plasma and lung lymph. The arterial oxygen tension decreased from 85 to 80 mm Hg (p < 0.05). The leukocyte count declined from 7854 to 6229/mm3 (p < 0.05), but this was not as low nor as prolonged as the interleukin-2 group. Further, the decrease in platelet count was prevented (p < 0.05). Interleukin-2 incubated with sheep or human leukocytes led to a dose-dependent increase in intracellular hydrogen peroxide production by neutrophils as measured by flow cytometry of dichlorofluorescin oxidation. These data indicate that interleukin-2 stimulates OFR generation and that OFR moderate the interleukin-2-induced increased lung permeability.

Original languageEnglish
Pages (from-to)169-175
Number of pages7
JournalSurgery
Volume109
Issue number2
StatePublished - Jan 1 1991

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    Klausner, J. M., Paterson, I. S., Goldman, G., Kobzik, L., Lelcuk, S., Skornick, Y., Eberlein, T., Valeri, C. R., Shepro, D., & Hechtman, H. B. (1991). Interleukin-2-induced lung injury is mediated by oxygen free radicals. Surgery, 109(2), 169-175.