Effects of interleukin-2 on the pulmonary microvasculature in anesthetized sheep.
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.
Lei
D
D
Department of Anesthesia, University of California, San Francisco 94143.
Jerome
E H
EH
Douguet
D
D
Jesmok
G J
GJ
Schuster
D P
DP
Johnson
C W
CW
Staub
N C
NC
D000818:Animals; D001773:Blood Cells / Q000166:cytology; D015633:Extravascular Lung Water / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology*; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008196:Lymph / Q000166:cytology / Q000378:metabolism; D008833:Microcirculation; D009994:Osmolar Concentration; D011652:Pulmonary Circulation / Q000187:drug effects*; D012756:Sheep; D013152:Splanchnic Circulation / Q000187:drug effects; D013897:Thoracic Duct / Q000378:metabolism
D007376:Interleukin-2