title: Circulating interleukin-1 receptor antagonist concentrations are increased in adult patients with thermal injury.
abstract: OBJECTIVE
  To investigate the balance between circulating concentrations of interleukin (IL)-1 and its natural inhibitor interleukin-1 receptor antagonist (IL-1Ra) in human inflammation.
  
  
  METHODS
  Prospective case-control study.
  
  
  METHODS
  University hospital burn care unit.
  
  
  METHODS
  Fifteen patients with second- or third-degree thermal injuries of 7% to 78% of total body surface and 15 healthy age- and sex-matched control subjects.
  
  
  METHODS
  None.
  
  
  RESULTS
  Median plasma IL-1Ra, but not IL-1 beta or tumor necrosis factor-alpha (TNF-alpha) concentrations were markedly increased on the day of admission in patients with thermal injuries compared with controls (1615 [range 426 to 23,800] vs. 494 [range 196 to 1093] pg/mL; p < .001). In survivors, the median IL-1Ra concentration normalized 12 to 21 days after admission. The concentration of IL-1Ra on the day of admission was weakly positively correlated to the extent and degree of thermal injury (r2 = .46; p < .05). IL-1Ra on days 1 to 3 was highest in three nonsurvivors with inhalation injuries compared with survivors (2166 [range 1362 to 36,624] vs. 1344 [range 665 to 13,085] pg/mL; p < .05). IL-1Ra increased significantly after debridement and skin transplantation (preoperatively 742 [range 488 to 1506] vs. postoperatively 1431 [range 1286 to 2107] pg/mL; p < .01). In nonsurvivors, median IL-1Ra was 3.6-fold higher than IL-1 beta on days 1 to 2 and 36-fold higher than IL-1 beta in three patients with bacteremia. IL-1Ra was studied for its relationship to previously reported parameters of the acute-phase response determined in the same samples from these patients. The increased concentrations of IL-1Ra coincided with a decrease in serum albumin concentration and increases in rectal temperature. However, IL-1Ra did not correlate with rectal temperature, plasma concentrations of endotoxin, IL-1 beta, or TNF-alpha either at admission or in follow-up samples.
  
  
  CONCLUSIONS
  Thermal injury causes an increase of circulating IL-1Ra, especially in patients with inhalation injuries. With the current plasma assays for IL-1 beta, IL-1Ra may be a more sensitive marker of human inflammation than IL-1 beta or TNF-alpha.
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Mandrup-Poulsen
authors.forename: L D
authors.initials: LD
authors.lastname: Wogensen
authors.forename: M
authors.initials: M
authors.lastname: Jensen
authors.forename: P
authors.initials: P
authors.lastname: Svensson
authors.forename: P
authors.initials: P
authors.lastname: Nilsson
authors.forename: T
authors.initials: T
authors.lastname: Emdal
authors.forename: J
authors.initials: J
authors.lastname: Mølvig
authors.forename: C A
authors.initials: CA
authors.lastname: Dinarello
authors.forename: J
authors.initials: J
authors.lastname: Nerup
mesh_terms: D000328:Adult; D002056:Burns / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D015601:Injury Severity Score; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012795:Sialoglycoproteins / Q000097:blood*; D015208:Smoke Inhalation Injury / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha