Journal of Applied Physiology, Vol 76, Issue 2 909-915, Copyright © 1994 by American Physiological Society
Effects of interleukin-2 on the pulmonary microvasculature in anesthetized sheep
D. Lei, E. H. Jerome, D. Douguet, G. J. Jesmok, D. P. Schuster, C. W. Johnson and N. C. Staub
Department of Anesthesia, University of California, San Francisco 94143.
Interleukin-2 (IL-2) is reputed to cause pulmonary microvascular injury. We
studied the pulmonary and splanchnic microcirculation of anesthetized sheep
after one dose (1.8 x 10(6) IU/kg) of IL-2 (n = 9) and after six doses (1.8
x 10(6) IU.kg-1.dose-1) of IL-2 over 3 days (n = 9). Seven control sheep
received only 5% dextrose diluent. We measured hemodynamics and lymph
dynamics in anesthetized sheep after the final dose of IL-2 or diluent.
After one dose of IL-2, caudal mediastinal node (mainly pulmonary) lymph
flow was stable, whereas thoracic duct lymph flow increased from a baseline
of 54 +/- 6 to 124 +/- 22 ml/h. After 3 days of IL-2, the caudal
mediastinal node lymph flow increased from 7.7 +/- 5.5 to 19.0 +/- 14.8
ml/h 5-6 h after the final dose of IL-2, and thoracic duct lymph flow
increased from 84 +/- 43 to 143 +/- 42 ml/h. The lymph-to-plasma protein
concentration ratio increased after IL-2 for thoracic duct but not for
caudal mediastinal node lymph. The equilibration rate of 125I-albumin from
plasma to caudal mediastinal node lymph did not change, whereas
plasma-to-thoracic duct lymph equilibration was faster after both one dose
and 3 days of IL-2. Positron emission tomography showed no increase in the
pulmonary transcapillary escape rate for 68Ga-labeled transferrin or in
extravascular lung water (n = 4). We conclude that IL-2 at doses two to
three times those used clinically does not significantly injure the
pulmonary microcirculation of sheep.
