Interleukin 1 production by human lung tissue. I. Identification and characterization

Crucial to the development of inflammatory infiltrates is the localized production of mediators which promote adherence of leukocytes to the vascular endothelium. Previous in vitro studies, using monolayers of cultured human vascular endothelial cells (VEC), have identified various agents which promote the acquisition of adhesiveness in VEC for polymorphonuclear leukocytes. In the present studies, we report that human lung fragments cultured for 4 to 24 hr release a factor which acts on VEC to promote adherence of polymorphonuclear leukocytes. Adhesiveness in VEC stimulated by lung fragment culture supernatants was time- and dose-dependent. This adherence-promoting factor appears to be a mixture of the alpha and beta forms of interleukin 1 (IL-1) and has the following properties: 1) it is heat-labile; 2) it is not inactivated by polymyxin B; 3) it has mobility on Sephadex G-75 column chromatography corresponding to apparent m.w. of approximately 15,000, 30,000, and 70,000 (a pattern observed previously for IL-1); 4) it has activity in the thymocyte costimulation IL-1 assay, but no interleukin 2 activity, and 5) it is neutralized by anti-human IL-1 antisera but not by anti-human tumor necrosis factor antiserum. Production and release of IL-1 in vivo may play a role in the development of inflammatory infiltrates in human lung and other tissues by acting on endothelium to promote the localized adherence of leukocytes.