CIRCULATING INTERLEUKIN-1 RECEPTOR ANTAGONIST CONCENTRATIONS ARE INCREASED IN ADULT PATIENTS WITH THERMAL-INJURY

Objective: To investigate the balance between circulating concentratio ns of interleukin (IL)-1 and its natural inhibitor interleukin-1 recep tor antagonist (IL-1Ra) in human inflammation. Design: Prospective cas e-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 cont rol subjects. Interventions: None. Measurements and Main Results: Medi an plasma IL-1Ra, but not IL-1 beta or tumor necrosis factor-alpha (TN F-alpha) concentrations were markedly increased on the day of admissio n in patients with thermal injuries compared with controls (1615 [rang e 426 to 23,800] vs. 494 [range 196 to 1093] pg/mL; p < .001). In surv ivors, the median IL-1Ra concentration normalized 12 to 21 days after admission. The concentration of IL-1Ra on the day of admission was wea kly positively correlated to the extent and degree of thermal injury ( r(2) = .46; P < .05). IL-1Ra on days 1 to 3 was highest in three nonsu rvivors with inhalation injuries compared with survivors (2166 [range 1362 to 36,624] vs. 1344 [range 665 to 13,085] pg/ mL; p < .05). IL-1R a 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 resp onse determined in the same samples from these patients. The increased concentrations of IL-1Ra coincided with a decrease in serum albumin c oncentration and increases in rectal temperature. However, IL-1Ra did not correlate with rectal temperature, plasma concentrations of endoto xin, IL-1 beta, or TNF-alpha either at admission or in follow-up sampl es. Conclusions: Thermal injury causes an increase of circulating IL-1 Ra, 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.