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Sepsis Induced by Cecal Ligation and Puncture

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Mouse Models of Innate Immunity

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1960))

Abstract

Despite advances in intensive care unit interventions, including the use of specific antibiotics and anti-inflammation treatment, sepsis with concomitant multiple organ failure is the most common cause of death in many acute care units. In order to understand the mechanisms of clinical sepsis and develop effective therapeutic modalities, there is a need to use effective experimental models that faithfully replicate what occurs in patients with sepsis. Several models are commonly used to study sepsis, including intravenous endotoxin challenge, injection of live organisms into the peritoneal cavity, establishing abscesses in the extremities, and the induction of experimental polymicrobial peritonitis via cecal ligation and puncture (CLP). Here, we describe the surgical procedure of CLP in mice, which has been demonstrated to closely replicate the nature and course of clinical sepsis in human subjects.

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References

  1. Glauser MP, Zanetti G, Baumgartner JD et al (1991) Septic shock: pathogenesis. Lancet 338:732–736

    Article  CAS  Google Scholar 

  2. Parrillo JE (1993) Pathogenetic mechanisms of septic shock. N Engl J Med 328:1471–1477

    Article  CAS  Google Scholar 

  3. Opal SM, Cohen J (1999) Clinical gram-positive sepsis: does it fundamentally differ from gram-negative bacterial sepsis? Crit Care Med 27:1608–1616

    Article  CAS  Google Scholar 

  4. Angus DC, Linde-Zwirble WT, Lidicker J et al (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303–1310

    Article  CAS  Google Scholar 

  5. Martin GS, Mannino DM, Eaton S et al (2003) The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 348:1546–1554

    Article  Google Scholar 

  6. Geerdes HF, Ziegler D, Lode H et al (1992) Septicemia in 980 patients at a university hospital in Berlin: prospective studies during 4 selected years between 1979 and 1989. Clin Infect Dis 15:991–1002

    Article  CAS  Google Scholar 

  7. Van Amersfoort ES, Van Berkel TJ, Kuiper J (2003) Receptors, mediators, and mechanisms involved in bacterial sepsis and septic shock. Clin Microbiol Rev 16:379–414

    Article  Google Scholar 

  8. Levy MM, Fink MP, Marshall JC et al (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS international Sepsis definitions conference. Intensive Care Med 29:530–538

    Article  Google Scholar 

  9. Riedemann NC, Guo RF, Ward PA (2003) The enigma of sepsis. J Clin Invest 112:460–467

    Article  CAS  Google Scholar 

  10. Tschoeke SK, Oberholzer A, Moldawer LL (2006) Interleukin-18: a novel prognostic cytokine in bacteria-induced sepsis. Crit Care Med 34:1225–1233

    Article  CAS  Google Scholar 

  11. Cavaillon JM, Adib-Conquy M, Fitting C et al (2003) Cytokine cascade in sepsis. Scand J Infect Dis 35:535–544

    Article  CAS  Google Scholar 

  12. Lin WJ, Yeh WC (2005) Implication of toll-like receptor and tumor necrosis factor alpha signaling in septic shock. Shock 24:206–209

    Article  CAS  Google Scholar 

  13. Lin KJ, Lin J, Hanasawa K et al (2000) Interleukin-8 as a predictor of the severity of bacteremia and infectious disease. Shock 14:95–100

    Article  CAS  Google Scholar 

  14. Coelho AL, Hogaboam CM, Kunkel SL (2005) Chemokines provide the sustained inflammatory bridge between innate and acquired immunity. Cytokine Growth Factor Rev 16:553–560

    Article  CAS  Google Scholar 

  15. Horn KD (1998) Evolving strategies in the treatment of sepsis and systemic inflammatory response syndrome (SIRS). QJM 91:265–277

    Article  CAS  Google Scholar 

  16. Karima R, Matsumoto S, Higashi H et al (1999) The molecular pathogenesis of endotoxic shock and organ failure. Mol Med Today 5:123–132

    Article  CAS  Google Scholar 

  17. Riedemann NC, Guo RF, Ward PA (2003) Novel strategies for the treatment of sepsis. Nat Med 9:517–524

    Article  CAS  Google Scholar 

  18. Davis CE, Brown KR, Douglas H et al (1969) Prevention of death from endotoxin with antisera. I. The risk of fatal anaphylaxis to endotoxin. J Immunol 102:563–572

    CAS  PubMed  Google Scholar 

  19. Beutler B, Milsark IW, Cerami AC (1985) Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 229:869–871

    Article  CAS  Google Scholar 

  20. Tracey KJ, Beutler B, Lowry SF et al (1986) Shock and tissue injury induced by recombinant human cachectin. Science 234:470–474

    Article  CAS  Google Scholar 

  21. Tracey KJ, Fong Y, Hesse DG et al (1987) Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature 330:662–664

    Article  CAS  Google Scholar 

  22. Ohlsson K, Bjork P, Bergenfeldt M et al (1990) Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. Nature 348:550–552

    Article  CAS  Google Scholar 

  23. Cohen J (1999) Adjunctive therapy in sepsis: a critical analysis of the clinical trial programme. Br Med Bull 55:212–225

    Article  CAS  Google Scholar 

  24. Reinhart K, Karzai W (2001) Anti-tumor necrosis factor therapy in sepsis: update on clinical trials and lessons learned. Crit Care Med 29:S121–S125

    Article  CAS  Google Scholar 

  25. Fisher CJ Jr, Agosti JM, Opal SM et al (1996) Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. The soluble TNF receptor Sepsis study group. N Engl J Med 334:1697–1702

    Article  CAS  Google Scholar 

  26. Fisher CJ Jr, Dhainaut JF, Opal SM et al (1994) Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis syndrome study group. JAMA 271:1836–1843

    Article  Google Scholar 

  27. Opal SM, Fisher CJ Jr, Dhainaut JF et al (1997) Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. The Interleukin-1 receptor antagonist Sepsis Investigator Group. Crit Care Med 25:1115–1124

    Article  CAS  Google Scholar 

  28. Bernard GR, Vincent JL, Laterre PF et al (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344:699–709

    Article  CAS  Google Scholar 

  29. Deitch EA (1998) Animal models of sepsis and shock: a review and lessons learned. Shock 9:1–11

    Article  CAS  Google Scholar 

  30. Parker SJ, Watkins PE (2001) Experimental models of gram-negative sepsis. Br J Surg 88:22–30

    Article  CAS  Google Scholar 

  31. Esmon CT (2004) Why do animal models (sometimes) fail to mimic human sepsis? Crit Care Med 32:S219–S222

    Article  Google Scholar 

  32. Maier S, Traeger T, Entleutner M et al (2004) Cecal ligation and puncture versus colon ascendens stent peritonitis: two distinct animal models for polymicrobial sepsis. Shock 21:505–511

    Article  Google Scholar 

  33. Hubbard WJ, Choudhry M, Schwacha MG et al (2005) Cecal ligation and puncture. Shock 24(Suppl 1):52–57

    Article  Google Scholar 

  34. Walley KR, Lukacs NW, Standiford TJ et al (1996) Balance of inflammatory cytokines related to severity and mortality of murine sepsis. Infect Immun 64:4733–4738

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Radojicic C, Andric B, Simovic M et al (1990) Genetic basis of resistance to trauma in inbred strains of mice. J Trauma 30:211–213

    Article  CAS  Google Scholar 

  36. von Stebut E, Udey MC (2004) Requirements for Th1-dependent immunity against infection with Leishmania major. Microbes Infect 6:1102–1109

    Article  Google Scholar 

  37. Sacks D, Noben-Trauth N (2002) The immunology of susceptibility and resistance to Leishmania major in mice. Nat Rev Immunol 2:845–858

    Article  CAS  Google Scholar 

  38. Benjamim CF, Hogaboam CM, Lukacs NW et al (2003) Septic mice are susceptible to pulmonary aspergillosis. Am J Pathol 163:2605–2617

    Article  Google Scholar 

  39. Benjamim CF, Lundy SK, Lukacs NW et al (2005) Reversal of long-term sepsis-induced immunosuppression by dendritic cells. Blood 105:3588–3595

    Article  CAS  Google Scholar 

  40. Wen H, Hogaboam CM, Gauldie J et al (2006) Severe sepsis exacerbates cell-mediated immunity in the lung due to an altered dendritic cell cytokine profile. Am J Pathol 168:1940–1950

    Article  CAS  Google Scholar 

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Acknowledgments

Haitao Wen is supported by the NIH grant R01GM120496.

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Correspondence to Haitao Wen .

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Gong, W., Wen, H. (2019). Sepsis Induced by Cecal Ligation and Puncture. In: Allen, I. (eds) Mouse Models of Innate Immunity. Methods in Molecular Biology, vol 1960. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9167-9_22

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  • DOI: https://doi.org/10.1007/978-1-4939-9167-9_22

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-9166-2

  • Online ISBN: 978-1-4939-9167-9

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