TUMOR-NECROSIS-FACTOR-ALPHA PLAYS A CENTRAL ROLE IN INTERLEUKIN-2-INDUCED PULMONARY VASCULAR LEAK AND LYMPHOCYTE ACCUMULATION

Administration of interleukin-2 (IL-2) leads to pulmonary vascular leak. This form of pulmonary edema has previously been postulated to be due to the in vivo induction of tumor necrosis factor-alpha (TNF-alpha). To determine whether TNF-alpha plays a role in IL-2-induced pulmonary vascular leak, we performed in situ hybridization of lung sections and reverse transcriptase-polymerase chain reaction of bronchoalveolar lavage macrophages from IL-2-challenged mice. The results confirm an in situ upregulation of TNF-alpha mRNA expression in the lungs associated with vascular leak. In addition, a significant increase in TNF-alpha protein production was found in the lung following IL2 administration, as measured by TNF-alpha-specific ELISA of lung supernatants (P = 0.028). Intravenous administration ofa soluble TNF receptor significantly diminished 1L-2-induced pulmonary vascular leak (P = 0.006). These findings confirm a central role for TNF-alpha in mediating the pulmonary vascular leak associated with IL-2 toxicity, (C) 1994 Academic Press, Inc.