CHRONIC INTERLEUKIN-2 TREATMENT IN AWAKE SHEEP CAUSES MINIMAL OR NO INJURY TO THE LUNG MICROVASCULAR BARRIER

Interleukin-2 (IL-2) is reputed to cause a ''vascular leak syndrome.'' We studied pulmonary hemodynamics and lymph dynamics in six sheep tre ated for 7 days with IL-2 (1.8 million IU/kg twice daily or 1.8 millio n 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 sev enth 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 equil ibration 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 cmH(2)O pre-IL-2, increased to 32 + 4 cmH(2)O on the fourth day of IL-2, and returned to 29 +/- 5 cmH(2)O 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 h emodynamic changes or to increased leakiness of the microvascular barr ier we volume loaded six sheep with lactated Ringer solution before an d after 3 days of IL-2 treatment (1.8 million IU/kg twice daily). Lung lymph flows increased fivefold during 4 h of crystalloid infusion com pared with baseline and were higher after 3 days of IL-2. However, lym ph-to-plasma protein concentration ratios decreased to the same low le vels 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 con clude that IL-2 causes minimal or no injury to the pulmonary microvasc ular barrier and that volume expansion during IL-2 treatment can cause hydrostatic pulmonary edema.