Abstract
Sepsis is amongst the world’s biggest public health problems with more than 20 million cases worldwide and a high morbidity rate of up to 50 %. Despite advances in modern medicine in the past few decades, incidence is expected to further increase due to an aging population and accompanying comorbidities such as cancer and diabetes. Due to the complexity of the disease, available treatment options are limited. Growing evidence links apoptotic cell death of lymphocytes and concomitant immune suppression to overall patient survival. In order to establish novel therapeutic approaches targeting this life threatening immune paralysis, researchers rely heavily on animal models to decipher the molecular mechanisms underlying this high impact disease. Here we describe variations of in vivo mouse models that can be used to study inflammation, cellular apoptosis, and survival in mice subjected to experimental polymicrobial sepsis and to a secondary infection during the immune suppressive secondary stage.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29(7):1303–1310
Hotchkiss RS, Coopersmith CM, McDunn JE, Ferguson TA (2009) The sepsis seesaw: tilting toward immunosuppression. Nat Med 15(5):496–497
Cohen J (2002) The immunopathogenesis of sepsis. Nature 420(6917):885–891
Schefold JC, Hasper D, Reinke P, Monneret G, Volk HD (2008) Consider delayed immunosuppression into the concept of sepsis. Crit Care Med 36(11):3118
Hotchkiss RS, Coopersmith CM, Karl IE (2005) Prevention of lymphocyte apoptosis—a potential treatment of sepsis? Clin Infect Dis 41(Suppl 7):S465–S469
Hotchkiss RS, Nicholson DW (2006) Apoptosis and caspases regulate death and inflammation in sepsis. Nat Rev Immunol 6(11):813–822
Drewry AM, Samra N, Skrupky LP, Fuller BM, Compton SM, Hotchkiss RS (2014) Persistent lymphopenia after diagnosis of sepsis predicts mortality. Shock 42(5):383–391
Nemzek JA, Hugunin KM, Opp MR (2008) Modeling sepsis in the laboratory: merging sound science with animal well-being. Comp Med 58(2):120–128
Muenzer JT, Davis CG, Chang K, Schmidt RE, Dunne WM, Coopersmith CM, Hotchkiss RS (2010) Characterization and Modulation of the Immunosuppressive Phase of Sepsis. Infect Immun 78(4):1582–1592
Shrum B, Anantha RV, Xu SX, Donnelly M, Haeryfar SM, McCormick JK, Mele T (2014) A robust scoring system to evaluate sepsis severity in an animal model. BMC Res Notes 7:233
Wichterman KA, Baue AE, Chaudry IH (1980) Sepsis and septic shock--a review of laboratory models and a proposal. J Surg Res 29(2):189–201
Baker CC, Chaudry IH, Gaines HO, Baue AE (1983) Evaluation of factors affecting mortality rate after sepsis in a murine cecal ligation and puncture model. Surgery 94(2):331–335
Dejager L, Pinheiro I, Dejonckheere E, Libert C (2011) Cecal ligation and puncture: the gold standard model for polymicrobial sepsis? Trends Microbiol 19(4):198–208. doi:10.1016/j.tim.2011.01.001
Chang KC, Unsinger J, Davis CG, Schwulst SJ, Muenzer JT, Strasser A, Hotchkiss RS (2007) Multiple triggers of cell death in sepsis: death receptor and mitochondrial-mediated apoptosis. FASEB J 21(3):708–719
Hotchkiss RS, Tinsley KW, Swanson PE, Chang KC, Cobb JP, Buchman TG, Korsmeyer SJ, Karl IE (1999) Prevention of lymphocyte cell death in sepsis improves survival in mice. Proc Natl Acad Sci U S A 96(25):14541–14546
Hotchkiss RS, Dunne WM, Swanson PE, Davis CG, Tinsley KW, Chang KC, Buchman TG, Karl IE (2001) Role of apoptosis in Pseudomonas aeruginosa pneumonia. Science 294(5548):1783
Brown RH, Walters DM, Greenberg RS, Mitzner W (1999) A method of endotracheal intubation and pulmonary functional assessment for repeated studies in mice. J Appl Physiol 87(6):2362–2365
Das S, MacDonald K, Chang HY, Mitzner W (2013) A simple method of mouse lung intubation. J Vis Exp 73:e50318
Starr ME, Steele AM, Saito M, Hacker BJ, Evers BM, Saito H (2014) A new cecal slurry preparation protocol with improved long-term reproducibility for animal models of sepsis. PLoS One 9(12):e115705
Acknowledgement
This work was supported by the Research Grant #1085281 from the National Health and Medical Research Council, Australia and a La Trobe University Postgraduate Research Scholarship to M.D.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer Science+Business Media New York
About this protocol
Cite this protocol
Doerflinger, M., Glab, J., Puthalakath, H. (2016). Experimental In Vivo Sepsis Models to Monitor Immune Cell Apoptosis and Survival in Laboratory Mice. In: Puthalakath, H., Hawkins, C. (eds) Programmed Cell Death. Methods in Molecular Biology, vol 1419. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3581-9_6
Download citation
DOI: https://doi.org/10.1007/978-1-4939-3581-9_6
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-3579-6
Online ISBN: 978-1-4939-3581-9
eBook Packages: Springer Protocols