INTERLEUKIN-6 PRODUCTION AFTER THERMAL-INJURY - EVIDENCE FOR NONMACROPHAGE SOURCES IN THE LUNG AND LIVER

Background. thermal injury induces circulating levels of interleukin-6 (IL-6). The liver and lung have been proposed as major sources of IL- 6 after injury; however, multiple cell types within these organs are c apable of IL-6 production. In these experiments we further characteriz e cellular sources of IL-6 after thermal injury by examining tissue ma crophage response in the liver and lung and IL-6 production of culture d pulmonary microvascular endothelial cells (PMECs). Methods. Serum, l iver and lung tissue, and tissue macrophage IL-6 response was determin ed in Wistar rats subjected to a 35 to 40% total body surface area sca ld injury. Cultured PMEC IL-6 production was determined after treatmen t with serum from the burned animals. IL-6 bioactivity was assayed by 7TD1 proliferation, and IL-6 messenger RNA levels were determined by r everse transcriptase-polymerase chain reaction. alveolar macrophages w ere obtained by bronchoalveolar lavage. Kupffer cells and PMECs were o btained by enzyme digestion of liver and lungs. Results. burn increase s circulating IL-6 activity through postburn day 3 (388 +/- 50 units/0 .1 ml versus 80 +/- 12 units/0.1 ml in controls). Burn increases lung and liver IL-6 messenger RNA without concurrent increase in the alveol ar macrophages or Kupffer cells and persists in the lung after broncho alveolar lavage. PMECs cultured in the presence of postburn day 3 seru m (10% vol) release more IL-6 activity (1118 +/- 333 units/culture ver sus sham rat serum with 288 +/- 146 units/culture) than control cultur es and have more readily detectable levels of IL-6 messenger RNA. Conc lusions. Non-tissue macrophage sources including microvascular endothe lium may be a contributing source of IL-6 in the lung after thermal in jury.