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 of studies investigating the cytokine levels in humans with inflammation-reperfusion injury in the absence of infection. Our hypothesis was that endotoxin is introduced into circulation during and after abdominal aortic aneurysm (AAA) repair and is associated with pro- and anti-inflammatory cytokine-response. The purpose of this prospective pilot study in 10 patients who underwent elective AAA repair was to assess organ function and immune response to systemic endotoxemia after the operation by measuring endotoxin, endotoxin neutralizing capacity (ENC), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and TNF-RI and II. Blood samples were obtained from indwelling catheters or direct venipuncture preoperatively, perioperatively (8 time points) until the second postoperative day. Endotoxin and ENC were determined by a special kinetic Limulus amoebocyte lysate (LAL) assay and TNF-alpha, IL-6, IL-10, and TNF-RI and II by commercial ELISA. Endotoxin levels were significantly elevated after declamping and 90 min after clamping of the aorta (2.3 + .9 pg/mL; 5.4+/-3.6 pg/mL). ENC decreased to the lowest levels at 90 min after clamping. TNF-alpha levels were maximal, but not significantly elevated, 120 min after clamping. IL-6 increased significantly during the operation and reached maximum levels (189.8+/-47 pg/mL) at the first postoperative day. Anti-inflammatory IL-10 and TNF-RI and II were elevated early during the operation. The changes in cytokine levels were associated with mild organ dysfunction. We conclude that AAA repair is associated with endotoxin, proinflammatory, and an almost coincidental anti-inflammatory cytokine release, providing baseline data about what constitutes an appropriate immune response. Such responses to trauma and ischemia-reperfusion need to be further investigated before attempting immunomodulation.
Holzheimer
R G
RG
Department of General Surgery, University of Halle, Germany. gresser.holzheimer@t-online.de
Gross
J
J
Schein
M
M
D000328:Adult; D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism / Q000628:therapy*; D016207:Cytokines / Q000096:biosynthesis*; D004731:Endotoxins / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008875:Middle Aged; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000628:therapy*; D010865:Pilot Projects; D012038:Regeneration / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D004731:Endotoxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10