Abstract
OBJECTIVE: This study investigates the course of serum cytokine levels in patients with multiple trauma, patients with a ruptured abdominal aortic aneurysm (AAA), and patients undergoing elective AAA repair and the relationship of these cytokines to the development of adult respiratory distress syndrome (ARDS) and multiple organ failure (MOF). SUMMARY BACKGROUND DATA: Severe tissue trauma, hemorrhagic shock, and ischemia-reperfusion injury are pathophysiologic mechanisms that may result in an excessive uncontrolled activation of inflammatory cells and mediators. This inflammatory response is thought to play a key role in the development of (remote) cell and organ dysfunction, which is the basis of ARDS and MOF. METHODS: The study concerns 28 patients with multiple trauma, 20 patients admitted in shock because of a ruptured AAA, and 18 patients undergoing elective AAA repair. Arterial blood was serially sampled from admission (or at the start of elective operation) to day 13 in the intensive care unit, and the serum concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and IL-6 were determined. RESULTS: Twenty-two patients died, 15 within 48 hours and 7 after several weeks, as a result of ARDS/MOF. At hospital admission and after 6 hours, these nonsurvivors had significantly higher plasma TNF-alpha and IL-1 beta levels than did the survivors. At the same measuring points, TNF-alpha and IL-1 beta were significantly more elevated in patients with ruptured AAA than in traumatized patients. However, IL-6 was significantly higher in the traumatized patients. In 10 patients, ARDS/MOF developed, and 41 had an uncomplicated course in this respect. Those with ARDS/MOF exhibited significantly different cytokine patterns in the early postinjury phase. TNF-alpha and IL-1 beta levels were higher mainly on the first day of admission; IL-6 concentrations were significantly elevated in patients with ARDS/MOF from the second day onward. The latter cytokine showed a good correlation with the daily MOF score during the whole 2-week observation period. CONCLUSIONS: In the early postinjury phase, higher concentrations of these cytokines are associated, not only with an increased mortality rate, but also with an increased risk for subsequent ARDS and MOF. These data therefore support the concept that these syndromes are caused by an overwhelming autodestructive inflammatory response.
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- Allgöwer M., Burri C. "Schockindex". Dtsch Med Wochenschr. 1967 Oct 27;92(43):1947–1950. doi: 10.1055/s-0028-1106070. [DOI] [PubMed] [Google Scholar]
- Ayala A., Wang P., Ba Z. F., Perrin M. M., Ertel W., Chaudry I. H. Differential alterations in plasma IL-6 and TNF levels after trauma and hemorrhage. Am J Physiol. 1991 Jan;260(1 Pt 2):R167–R171. doi: 10.1152/ajpregu.1991.260.1.R167. [DOI] [PubMed] [Google Scholar]
- Baigrie R. J., Lamont P. M., Dallman M., Morris P. J. The release of interleukin-1 beta (IL-1) precedes that of interleukin 6 (IL-6) in patients undergoing major surgery. Lymphokine Cytokine Res. 1991 Aug;10(4):253–256. [PubMed] [Google Scholar]
- Baker S. P., O'Neill B., Haddon W., Jr, Long W. B. The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care. J Trauma. 1974 Mar;14(3):187–196. [PubMed] [Google Scholar]
- Billiau A., Vandekerckhove F. Cytokines and their interactions with other inflammatory mediators in the pathogenesis of sepsis and septic shock. Eur J Clin Invest. 1991 Dec;21(6):559–573. doi: 10.1111/j.1365-2362.1991.tb01410.x. [DOI] [PubMed] [Google Scholar]
- Bitterman H., Kinarty A., Lazarovich H., Lahat N. Acute release of cytokines is proportional to tissue injury induced by surgical trauma and shock in rats. J Clin Immunol. 1991 Jul;11(4):184–192. doi: 10.1007/BF00917424. [DOI] [PubMed] [Google Scholar]
- Bone R. C., Sibbald W. J., Sprung C. L. The ACCP-SCCM consensus conference on sepsis and organ failure. Chest. 1992 Jun;101(6):1481–1483. doi: 10.1378/chest.101.6.1481. [DOI] [PubMed] [Google Scholar]
- Cannon J. G., Tompkins R. G., Gelfand J. A., Michie H. R., Stanford G. G., van der Meer J. W., Endres S., Lonnemann G., Corsetti J., Chernow B. Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever. J Infect Dis. 1990 Jan;161(1):79–84. doi: 10.1093/infdis/161.1.79. [DOI] [PubMed] [Google Scholar]
- Cannon J. G., van der Meer J. W., Kwiatkowski D., Endres S., Lonnemann G., Burke J. F., Dinarello C. A. Interleukin-1 beta in human plasma: optimization of blood collection, plasma extraction, and radioimmunoassay methods. Lymphokine Res. 1988 Winter;7(4):457–467. [PubMed] [Google Scholar]
- Caty M. G., Guice K. S., Oldham K. T., Remick D. G., Kunkel S. I. Evidence for tumor necrosis factor-induced pulmonary microvascular injury after intestinal ischemia-reperfusion injury. Ann Surg. 1990 Dec;212(6):694–700. doi: 10.1097/00000658-199012000-00007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cerami A. Inflammatory cytokines. Clin Immunol Immunopathol. 1992 Jan;62(1 Pt 2):S3–10. doi: 10.1016/0090-1229(92)90035-m. [DOI] [PubMed] [Google Scholar]
- Cruickshank A. M., Fraser W. D., Burns H. J., Van Damme J., Shenkin A. Response of serum interleukin-6 in patients undergoing elective surgery of varying severity. Clin Sci (Lond) 1990 Aug;79(2):161–165. doi: 10.1042/cs0790161. [DOI] [PubMed] [Google Scholar]
- Damas P., Ledoux D., Nys M., Vrindts Y., De Groote D., Franchimont P., Lamy M. Cytokine serum level during severe sepsis in human IL-6 as a marker of severity. Ann Surg. 1992 Apr;215(4):356–362. doi: 10.1097/00000658-199204000-00009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Deitch E. A. Multiple organ failure. Pathophysiology and potential future therapy. Ann Surg. 1992 Aug;216(2):117–134. doi: 10.1097/00000658-199208000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dinarello C. A., Mier J. W. Lymphokines. N Engl J Med. 1987 Oct 8;317(15):940–945. doi: 10.1056/NEJM198710083171506. [DOI] [PubMed] [Google Scholar]
- Endres S., Cannon J. G., Ghorbani R., Dempsey R. A., Sisson S. D., Lonnemann G., Van der Meer J. W., Wolff S. M., Dinarello C. A. In vitro production of IL 1 beta, IL 1 alpha, TNF and IL2 in healthy subjects: distribution, effect of cyclooxygenase inhibition and evidence of independent gene regulation. Eur J Immunol. 1989 Dec;19(12):2327–2333. doi: 10.1002/eji.1830191222. [DOI] [PubMed] [Google Scholar]
- Ertel W., Faist E., Nestle C., Hueltner L., Storck M., Schildberg F. W. Kinetics of interleukin-2 and interleukin-6 synthesis following major mechanical trauma. J Surg Res. 1990 Jun;48(6):622–628. doi: 10.1016/0022-4804(90)90242-t. [DOI] [PubMed] [Google Scholar]
- Faist E., Mewes A., Strasser T., Walz A., Alkan S., Baker C., Ertel W., Heberer G. Alteration of monocyte function following major injury. Arch Surg. 1988 Mar;123(3):287–292. doi: 10.1001/archsurg.1988.01400270021002. [DOI] [PubMed] [Google Scholar]
- Ghezzi P., Dinarello C. A., Bianchi M., Rosandich M. E., Repine J. E., White C. W. Hypoxia increases production of interleukin-1 and tumor necrosis factor by human mononuclear cells. Cytokine. 1991 May;3(3):189–194. doi: 10.1016/1043-4666(91)90015-6. [DOI] [PubMed] [Google Scholar]
- Goris R. J., te Boekhorst T. P., Nuytinck J. K., Gimbrère J. S. Multiple-organ failure. Generalized autodestructive inflammation? Arch Surg. 1985 Oct;120(10):1109–1115. doi: 10.1001/archsurg.1985.01390340007001. [DOI] [PubMed] [Google Scholar]
- Knaus W. A., Draper E. A., Wagner D. P., Zimmerman J. E. APACHE II: a severity of disease classification system. Crit Care Med. 1985 Oct;13(10):818–829. [PubMed] [Google Scholar]
- Levine B., Kalman J., Mayer L., Fillit H. M., Packer M. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med. 1990 Jul 26;323(4):236–241. doi: 10.1056/NEJM199007263230405. [DOI] [PubMed] [Google Scholar]
- Marano M. A., Fong Y., Moldawer L. L., Wei H., Calvano S. E., Tracey K. J., Barie P. S., Manogue K., Cerami A., Shires G. T. Serum cachectin/tumor necrosis factor in critically ill patients with burns correlates with infection and mortality. Surg Gynecol Obstet. 1990 Jan;170(1):32–38. [PubMed] [Google Scholar]
- Moore F. A., Moore E. E., Poggetti R., McAnena O. J., Peterson V. M., Abernathy C. M., Parsons P. E. Gut bacterial translocation via the portal vein: a clinical perspective with major torso trauma. J Trauma. 1991 May;31(5):629–638. doi: 10.1097/00005373-199105000-00006. [DOI] [PubMed] [Google Scholar]
- Pepe P. E., Potkin R. T., Reus D. H., Hudson L. D., Carrico C. J. Clinical predictors of the adult respiratory distress syndrome. Am J Surg. 1982 Jul;144(1):124–130. doi: 10.1016/0002-9610(82)90612-2. [DOI] [PubMed] [Google Scholar]
- Roumen R. M., Hendriks T., Wevers R. A., Goris J. A. Intestinal permeability after severe trauma and hemorrhagic shock is increased without relation to septic complications. Arch Surg. 1993 Apr;128(4):453–457. doi: 10.1001/archsurg.1993.01420160095016. [DOI] [PubMed] [Google Scholar]
- Roumen R. M., van Meurs P. A., Kuypers H. H., Kraak W. A., Sauerwein R. W. Serum interleukin-6 and C reactive protein responses in patients after laparoscopic or conventional cholecystectomy. Eur J Surg. 1992 Oct;158(10):541–544. [PubMed] [Google Scholar]
- Rush B. F., Jr, Sori A. J., Murphy T. F., Smith S., Flanagan J. J., Jr, Machiedo G. W. Endotoxemia and bacteremia during hemorrhagic shock. The link between trauma and sepsis? Ann Surg. 1988 May;207(5):549–554. doi: 10.1097/00000658-198805000-00009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schlüter B., König B., Bergmann U., Müller F. E., König W. Interleukin 6--a potential mediator of lethal sepsis after major thermal trauma: evidence for increased IL-6 production by peripheral blood mononuclear cells. J Trauma. 1991 Dec;31(12):1663–1670. doi: 10.1097/00005373-199112000-00017. [DOI] [PubMed] [Google Scholar]
- Stylianos S., Wakabayashi G., Gelfand J. A., Harris B. H. Experimental hemorrhage and blunt trauma do not increase circulating tumor necrosis factor. J Trauma. 1991 Aug;31(8):1063–1067. [PubMed] [Google Scholar]
- Takayama T. K., Miller C., Szabo G. Elevated tumor necrosis factor alpha production concomitant to elevated prostaglandin E2 production by trauma patients' monocytes. Arch Surg. 1990 Jan;125(1):29–35. doi: 10.1001/archsurg.1990.01410130031004. [DOI] [PubMed] [Google Scholar]
- Trautinger F., Hammerle A. F., Pöschl G., Micksche M. Respiratory burst capability of polymorphonuclear neutrophils and TNF-alpha serum levels in relationship to the development of septic syndrome in critically ill patients. J Leukoc Biol. 1991 May;49(5):449–454. doi: 10.1002/jlb.49.5.449. [DOI] [PubMed] [Google Scholar]
- van Deventer S. J., Knepper A., Landsman J., Lawson J., ten Cate J. W., Buller H. R., Sturk A., Pauw W. Endotoxins in portal blood. Hepatogastroenterology. 1988 Oct;35(5):223–225. [PubMed] [Google Scholar]
