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 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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
Non-tissue macrophage sources including microvascular endothelium may be a contributing source of IL-6 in the lung after thermal injury.
Bankey
P E
PE
University of Texas Southwestern Medical Center, Dallas, USA.
Williams
J G
JG
Guice
K S
KS
Taylor
S N
SN
D000818:Animals; D001483:Base Sequence; D001681:Biological Assay; D002056:Burns / Q000097:blood / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011652:Pulmonary Circulation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic
D015850:Interleukin-6; D008070:Lipopolysaccharides; D015335:Molecular Probes; D012333:RNA, Messenger