Effects of PEG-coupled interleukin-2 on rat lung lavage parameters

The recombinant lymphokine interleukin-2 (IL-2) has activity in renal cell carcinoma, melanoma, and other cancers. A side effect of IL-2 use is a "capillary leak phenomenon" which is purported to be related to endothelial effects of IL-2 itself or to cells activated by IL-2. We studied IL-2 effects on rat lung lavage parameters to determine whether endothelial damage occurred. The specific endpoints were 125I-albumin extravasation, lavage protein, and lavage angiotensin-converting enzyme (ACE) activity. To ensure sensitivity of these endpoints, we used the known endothelial toxicant thiourea, which increases lung lavage protein and lavage ACE. We found that both PEG IL-2 and thiourea increased the amount of protein and 125-I flux into the lavage. However, although thiourea increased lavage ACE, PEG IL-2 did not. These results suggest that PEG IL-2 can increase protein and iodine flux across the endothelium without causing cell injury.