Soluble Cytokine Receptors and Receptor Antagonists Are Sequentially Released after Trauma

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Abstract
Cytokine receptors and receptor antagonists (RAs) have been identified in trauma patients. We hypothesized that after traumatic injury, a sequential release of soluble cytokine receptors and RAs may exist that mirrors the release of the primary cytokines themselves. Twenty-two patients were included in the study: 14 males and 8 females. The mean age was 30.1 +/- 12.5 (range, 19 to 71), and the mean Injury Severity Score was 28.7 +/- 12.6 (range, 4 to 57). There were 15 survivors and 7 nonsurvivors. Samples were collected on arrival to the emergency department and at serial intervals for up to 7 days. Monoclonal antibody enzyme-linked immunosorbent assay kits to tumor necrosis factor (TNF), soluble TNF-receptor (sTNF-R) 55 kd and 75 kd, interleukin (IL)-1 and IL-1 RA, and IL-2 and IL-2r were used. Sera from 22 healthy individuals were used as normal controls. No TNF, IL-1, or IL-2 could be detected in any patient sera after injury. Control levels for the soluble cytokine receptors and RAs were as follows: sTNF-R 55 kd, 607 +/- 89 pg/mL; sTNF-R 75 kd, 2,141 +/- 169 pg/mL; IL-1 RA, 291 +/- 35 pg/mL; and IL-2r, 426 +/- 53 U/mL. In trauma patients, both 55 kd and 75 kd sTNF-R were significantly elevated on arrival to the emergency department, with values of 2,441 +/- 506 pg/mL (p < 0.001) and 4,736 +/- 537 pg/mL (p < 0.001), respectively. Although IL-1 RAs were also significantly elevated on arrival to the emergency department, serum levels continued to rise, peaking 4 to 6 hours after injury, with values of 58,257 +/- 22,841 pg/mL (p < 0.005). In contrast, IL-2r levels peaked later, with values at 7 to 12 hours, 624 +/- 71 U/mL (p < 0.05); at day 1,757 +/- 51 U/mL (p < 0.001); at day 4, 1,063 +/- 217 U/mL (p < 0.001); and at day 7, 2,337 +/- 815 U/mL (p < 0.001). These data suggest a sequential release of cytokine receptors and RAs, despite the absence of detectable levels of the primary cytokines themselves. A previously unrecognized physiologic mechanism may exist that regulates cytokine receptor and RA release after injury.