Pro- and anti-inflammatory cytokine-response in abdominal aortic aneurysm repair: A clinical model of ischemia-reperfusion

In traumatized and septic patients, excessive cytokine production may lead to organ dysfunction and death. Current understanding of cytokine kinetics with regard to clinical scenarios, however, is still limited by a paucity o f studies investigating the cytokine levels in humans with inflammation-rep erfusion injury in the absence of infection, Our hypothesis was that endoto xin is introduced into circulation during and after abdominal aortic aneury sm (AAA) repair and is associated with pro- and anti-inflammatory cytokine- response. The purpose of this prospective pilot study in 10 patients who un derwent elective AAA repair was to assess organ function and immune respons e to systemic endotoxemia after the operation by measuring endotoxin, endot oxin neutralizing capacity (ENC), tumor necrosis factor (TNF)-alpha, interl eukin (IL)-6, IL-10, and TNF-RI and II. Blood samples were obtained from in dwelling catheters or direct venipuncture preoperatively, perioperatively ( 8 time points) until the second postoperative day. Endotoxin and ENC were d etermined by a special kinetic Limulus amoebocyte lysate (LAL) assay and TN F-alpha, IL-6, IL-10, and TNF-RI and II by commercial ELISA. Endotoxin leve ls were significantly elevated after declamping and 90 min after clamping o f the aorta (2.3 + .9 pg/mL; 5.4 +/- 3.6 pg/ml). ENC decreased to the lowes t levels at 90 min after clamping. TNF-alpha levels were maximal, but not s ignificantly elevated, 120 min after clamping. IL-6 increased significantly during the operation and reached maximum levels (189.8 +/- 47 pg/ml) at th e first postoperative day. Anti-inflammatory IL-10 and TNF-RI and II were e levated early during the operation. The changes in cytokine levels were ass ociated with mild organ dysfunction. We conclude that AAA repair is associa ted with endotoxin, proinflammatory, and an almost coincidental anti-inflam matory cytokine release, providing baseline data about what constitutes an appropriate immune response. Such responses to trauma and ischemia-reperfus ion need to be further investigated before attempting immunomodulation.