Chronic interleukin-2 treatment in awake sheep causes minimal or no injury to the lung microvascular barrier

Jerome, E. Heidi, Keiji Enzan, Dominique Douguet, DachuanLei, Gary Jesmok, Carol W. Johnson, Maritza Neuburger, and Norman C. Staub. Chronic interleukin-2 treatment in awake sheep causes minimal or no injury to the lung microvascular barrier.J. Appl. Physiol. 81(4):1730-1738, 1996.Interleukin-2 (IL-2) is reputed tocause a "vascular leak syndrome." We studied pulmonaryhemodynamics and lymph dynamics in six sheep treated for 7 days withIL-2 (1.8 million IU/kg twice daily or 1.8 million IU/kg each day as acontinuous infusion). Lung lymph flow increased from 4.8 ± 2 ml/15min pre-IL-2 to 14.4 ± 6.8 ml/15 min on the seventh day of IL-2.The lymph-to-plasma protein concentration ratio was unchanged (0.70 ± 0.06 vs. 0.63 ± 0.13). The plasma-to-lymph equilibrationhalf-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 cmH₂O pre-IL-2, increased to 32 ± 4 cmH₂O on the fourth day ofIL-2, and returned to 29 ± 5 cmH₂O on the seventh day of IL-2.Extravascular lung water was normal (4.07 ± 0.25 g/g dry lung). Toclearly determine whether the increase in lung lymph flow was due tohemodynamic changes or to increased leakiness of the microvascularbarrier, we volume loaded six sheep with lactated Ringer solutionbefore and after 3 days of IL-2 treatment (1.8 million IU/kg twicedaily). Lung lymph flows increased fivefold during 4 h of crystalloidinfusion compared with baseline and were higher after 3 days of IL-2.However, lymph-to-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 thepulmonary microvascular barrier and that volume expansion during IL-2treatment can cause hydrostatic pulmonary edema.