Interleukin-6 production after thermal injury: evidence for nonmacrophage sources in the lung and liver.

Abstract

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 capable of IL-6 production. In these experiments we further characterize cellular sources of IL-6 after thermal injury by examining tissue macrophage response in the liver and lung and IL-6 production of cultured pulmonary microvascular endothelial cells (PMECs). Serum, liver and lung tissue, and tissue macrophage IL-6 response was determined in Wistar rats subjected to a 35 to 40% total body surface area scald injury. Cultured PMEC IL-6 production was determined after treatment with serum from the burned animals. IL-6 bioactivity was assayed by 7TD1 proliferation, and IL-6 messenger RNA levels were determined by reverse transcriptase-polymerase chain reaction. Alveolar macrophages were obtained by bronchoalveolar lavage. Kupffer cells and PMECs were obtained by enzyme digestion of liver and lungs. Burn increases 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 alveolar macrophages or Kupffer cells and persists in the lung after bronchoalveolar lavage. PMECs cultured in the presence of postburn day 3 serum (10% vol) release more IL-6 activity (1118 +/- 333 units/culture versus sham rat serum with 288 +/- 146 units/culture) than control cultures and have more readily detectable levels of IL-6 messenger RNA. Non-tissue macrophage sources including microvascular endothelium may be a contributing source of IL-6 in the lung after thermal injury.