Tumor Necrosis Factor-α 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-α (TNF-α). To determine whether TNF-α 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-α mRNA expression in the lungs associated with vascular leak. In addition, a significant increase in TNF-α protein production was found in the lung following IL-2 administration, as measured by TNF-α-specific ELISA of lung supernatants (P = 0.028). Intravenous administration of a soluble TNF receptor significantly diminished IL-2-induced pulmonary vascular leak (P = 0.006). These findings confirm a central role for TNF-α in mediating the pulmonary vascular leak associated with IL-2 toxicity.