Cytokines and adhesion molecules in elective and accidental trauma-related ischemia/reperfusion

The major pathophysiologic role of cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and IL-6, as well as of the (soluble) adhesion molecules ICAM-1 and E-selectin, has been identified using different experimental models of ischemia/reperfusion injury. Moreover, in intensive care management, evaluation of these agents as diagnostic or prognostic tools is of great interest in ischemia/reperfusion injury caused by surgical or accidental trauma. For this reason, inflammatory mediators including those mentioned above were investigated in three different groups of surgical patients.

The first group (A, n = 13) comprised patients undergoing elective limb surgery without a tourniquet. The second group (B, n = 36) included patients subjected to limb surgery with a tourniquet. The third group (C, n = 30) was composed of accidental trauma patients who were retrospectively divided into those with and without multiple organ dysfunction (+MOD and -MOD, respectively) as defined by the Denver Score. Serial blood samples were taken during a 5-day (elective surgery) or 14-day (accidental trauma) observation period for monitoring of cytokines and soluble adhesion molecules. The clinical course and the degree of MOD were recorded daily.

Only when a tourniquet was applied for a mean time of 105 minutes did elective limb surgery result in significantly increased serum levels of IL-6, IL,-1ra, and IL-10 but not TNF-RII. Yet, the increase in cytokine levels was not sufficient to cause an enhanced shedding of adhesion molecules, and both soluble ICAM-1 and soluble E-selectin remained unchanged in groups A and B throughout the 5-day observation period. In patients with multiple injuries (group C), all parameters increased early after trauma up to 10- to 20-fold in comparison with the elective limb surgery patients in groups A and B. When the accidental trauma patients were divided according to the Denver Score for +MOD (n = 8, mean Injury Severity Score = 33.8) and -MOD (n = 22, mean Injury Severity Score = 31.2), a clear difference became evident in serum IL-6 and IL-1ra levels within the first 4 days and in serum IL-10 levels for the first 2 days after trauma, with cytokine levels being significantly higher in the +MOD patients 3 to 4 days before the onset of MOD. Although highly elevated, TNF-RII levels did not differentiate between +MOD and -MOD at any time. The increase in serum cytokine levels was associated with a remarkable expression and shedding of ICAM-1 and E-selectin made obvious by significantly increased soluble serum ICAM-1 levels in +MOD patients compared with the -MOD group between days 3 and 5 after trauma and increased soluble serum E-selectin levels between days 2 and 4 after trauma.

The release of cytokines and soluble adhesion molecules into the circulation correlates well with the degree of trauma (elective surgery vs. accidental multiple trauma), depending on the extent of the associated ischemia/reperfusion injury. Both groups of mediators are also clearly related to the development of MOD in patients with multiple injuries with generalized ischemia/reperfusion injury caused by hemorrhagic shock. They may be predictive of patients at risk for MOD when measured early in the posttraumatic period.