Circulating interleukin-1 receptor antagonist concentrations are increased in adult patients with thermal injury.

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. DESIGN: Prospective case-control study. SETTING: University hospital burn care unit. PATIENTS: 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. INTERVENTIONS: None. MEASUREMENTS AND MAIN 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.