Chronic interleukin-2 treatment in awake sheep causes minimal or no injury to the lung microvascular barrier. Jerome, E. Heidi, Keiji Enzan, Dominique Douguet, Dachuan Lei, Gary Jesmok, Carol W. Johnson, Maritza Neuburger, Norman C. Staub. Cardiovascular Research Institute, Departments of Anesthesia, Medicine and Physiology and Cetus Corporation, Emeryville, CA (PH, GJ and CWJ)
APStracts 3:0258A, 1996.
Interleukin-2 is reputed to cause a "vascular leak syndrome". We studied pulmonary hemodynamics and lymph dynamics in six sheep treated for seven days with IL-2 (1.8 million IU/kg twice daily or 1.8 million IU/kg each day as a continuous infusion). Lung lymph flow increased from 4.8+/-2 ml/15 min pre-IL-2 to 14.4+/-6.8 ml/15 min on the seventh day of IL-2. Lymph/plasma protein concentration ratio was unchanged (0.70+/-0.06 vs 0.63+/-0.13). The plasma-to-lymph equilibration half-time of radiolabeled albumin was 2.0+/-0.6 h pre -IL-2 and 1.0+/-0.7 h on day 7 of IL-2. Pulmonary arterial pressure was 24+/-7 cm H2O pre-IL-2, increased to 32+/-4 cm H2O on the fourth day of IL-2 and returned to 29+/-5 cm H2O on the seventh day of IL-2. Extravascular lung water was normal (4.07+/-0.25 g/g dry lung). To clearly determine whether the increase in lung lymph flow was due to hemodynamic changes or to increased leakiness of the microvascular barrier, we volume-loaded six sheep with lactated Ringer's solution before and after three days of IL-2 treatment (1.8 million IU/kg twice daily). Lung lymph flows increased five-fold during 4 h of crystalloid infusion compared to baseline and were higher after three days of IL-2. However, lymph/plasma protein concentration ratios decreased to the same low levels pre- and post-IL-2 (0.39+/-0.06 vs 0.41+/-0.10), indicating an intact microvascular barrier. Extravascular lung water was elevated (5.56+/-0.39 g/g dry lung) but was not different from lung water in three volume-loaded control sheep (4.87+/-0.53 g/g dry lung). We conclude that IL-2 causes minimal or no injury to the pulmonary microvascular barrier and that volume expansion during IL-2 treatment can cause hydrostatic pulmonary edema. 

Received 12 May 1995; accepted in final form 15 November 1995.
APS Manuscript Number A498-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 June 96