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 IL-2 administration, as measured by TNF-alpha-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-alpha in mediating the pulmonary vascular leak associated with IL-2 toxicity.
UCLA-Wadsworth Pulmonary Immunology Laboratory, Division of Pulmonary Medicine, West Los Angeles VA Medical Center 90073.
S M
SM
Dubinett
M
M
Huang
A
A
Lichtenstein
W H
WH
McBride
J
J
Wang
G
G
Markovitz
D
D
Kelley
W W
WW
Grody
L E
LE
Mintz
S
S
Dhanani
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D005260:Female; D017403:In Situ Hybridization; D007376:Interleukin-2 / Q000633:toxicity*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D011654:Pulmonary Edema / Q000139:chemically induced / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D011994:Recombinant Proteins / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology*; D015854:Up-Regulation
D007376:Interleukin-2; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha