Mixed agonistic-antagonistic cytokine response in whole blood from patients undergoing abdominal aortic aneurysm repair

• Published in: Intensive care medicine 1999-03, Vol.25 (3), p.279-287
• Main Authors: ZIEGENFUSS, T, WANNER, G. A, GRASS, C, BAUER, I, SCHÜDER, G, KLEINSCHMIDT, S, MENGER, M. D, BAUER, M
• Format: Article
• Language: English
• Subjects: Abdomen; Aged; Analysis of Variance; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Aneurysm; Aortic Aneurysm, Abdominal - blood; Aortic Aneurysm, Abdominal - surgery; Aortic aneurysms; Biological and medical sciences; Blotting, Northern; Cytokines; Cytokines - genetics; Cytokines - metabolism; Emergency and intensive postoperative care (general aspects). Pathophysiology of surgery; Female; Fentanyl; Gene expression; Gene Expression Regulation; Hernias; Humans; Intensive care medicine; Intraoperative Period; Ischemia; Lipopolysaccharides - metabolism; Male; Medical sciences; Middle Aged; Multiple organ dysfunction syndrome; Pilot projects; Prospective Studies; RNA - analysis; Surgery; Trauma; Tumor necrosis factor-TNF
• ISSN: 0342-4642; 1432-1238
• DOI: 10.1007/s001340050836

To characterize the impact of abdominal aortic aneurysm repair (AAAR) on spontaneous as well as lipopolysaccharide (LPS)-induced gene expression of pro- and anti-inflammatory cytokines. Prospective, controlled in vivo/ex vivo study. University hospital. Whole blood from 14 consecutive patients undergoing AAAR withdrawn prior to surgery (T1), at the end of ischemia (T2), 90 min after declamping (T3) and on the first postoperative day (T4) was cultured in the absence or presence of LPS. Five patients undergoing elective inguinal hernia repair served as controls. While tumor necrosis factor (TNF), Interleukin (IL)-1 and IL-10 plasma concentrations did not increase significantly, IL-6 was elevated at each time point, as compared with T1. Despite the spontaneous release of trace amounts of IL-6, the ability of cultured whole blood to mount a cytokine response in vitro to LPS was impaired for all cytokines studied at T2 (TNF-62%, IL-1-51%, IL-6 -20%, IL-10-51%). The stimulated IL-6 response was restored early after declamping (T3: +56 %) and enhanced 1 day after operation (T4: +144%). In contrast, stimulated TNF and IL-1 responses remained depressed at T3 (TNF -48%, IL-1-64%) and T4 (TNF-40%, IL-1-24%). A biphasic pattern was observed for IL-10 with initial depression at T3 (-51%) and restoration at T4 (+40%). Among the different cytokines monitored, only impaired TNF responsiveness at early reperfusion (T3) correlated with the postoperative course, as reflected by APACHE II. Cytokine response to LPS was maintained or even increased during and after surgery in the whole blood from patients undergoing hernia repair. Despite consistent development of clinical signs of systemic inflammatory response syndrome (SIRS) and spontaneous release of IL-6 abdominal aortic aneurysm repair produces a state of impaired pro-inflammatory cytokine response upon a subsequent in vitro Gram-negative stimulus. This early impairment of TNF responsiveness seems to correlate with an unfavorable postoperative course.