Objective: To determine the effects of accidental injury of varying se
verity on interleukin (IL)-1alpha, IL-6, IL-8, tumor necrosis factor-a
lpha (TNF-alpha), and endotoxin release. Design: Prospective, multi-un
it, longitudinal study. Setting: Emergency Departments and intensive c
are units of two university hospitals. Patients: Trauma patients after
mild, moderate, and severe injury (Injury Severity Score of less-than
-or-equal-to 10, 11 to 24, and greater-than-or-equal-to 25, respective
ly). Interventions: None. Measurements and Main Results: Plasma cytoki
ne and endotoxin concentrations were measured over a 5-day period, sta
rting within 2 hrs of accidental injury. An enzyme-linked immunosorben
t assay was used to determine plasma concentrations of IL-1alpha, EL-6
, IL-8, and TNF-alpha. Plasma endotoxin concentrations were measured u
sing a chromogenic limulus amebocyte assay. Preresuscitation samples o
btained immediately on arrival in the Emergency Department, and within
2 hrs of injury, demonstrated significant increases of IL-6 and IL-8
concentrations in the severe injury group, in contrast to minimal incr
eases seen after mild or moderate injury. Analysis of serial postresus
citation samples demonstrated rapid increases in IL-6 and IL-8 concent
rations within 12 hrs of injury. IL-6 and IL-8 remained increased for
24 hrs after injury, then decreased markedly from their peak values du
ring the next 24 hrs. Increased circulating concentrations of these cy
tokines continued to be present for >5 days in the severely injured pa
tients. IL-6 and IL-8 concentrations were only minimally increased in
patients 8 and 24 hrs after moderate injury. Endotoxin and IL-1alpha w
ere not found in any samples, including those samples obtained seriall
y from severely injured patients. No patient at any time point had TNF
-alpha concentrations of >35 pg/mL. Conclusions: These results demonst
rate that severe injury produces rapid, large increases in circulating
concentrations of IL-6 and IL-8 that may contribute to the frequent d
evelopment of the adult respiratory distress syndrome and multiple org
an system failure in this clinical setting.