Host Responses to Sepsis Vary in Different Low-Lethality Murine Models

被引:33
作者
Gentile, Lori F. [1 ]
Nacionales, Dina C. [1 ]
Lopez, M. Cecilia [2 ]
Vanzant, Erin [1 ]
Cuenca, Angela [1 ]
Szpila, Benjamin E. [1 ]
Cuenca, Alex G. [1 ]
Joseph, Anna [3 ]
Moore, Frederick A. [1 ]
Leeuwenburgh, Christiaan [3 ]
Baker, Henry V. [2 ]
Moldawer, Lyle L. [1 ]
Efron, Philip A. [1 ]
机构
[1] Univ Florida, Coll Med, Dept Surg, Gainesville, FL 32611 USA
[2] Univ Florida, Coll Med, Gainesville, FL USA
[3] Univ Florida, Coll Med, Inst Aging, Gainesville, FL USA
关键词
LABORATORY MODELS; ANIMAL-MODELS; IMMUNOSUPPRESSION; INFLAMMATION; INTERFERON; MORTALITY; IMMUNITY; MOUSE; SHOCK;
D O I
10.1371/journal.pone.0094404
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Introduction: Animal models for the study of sepsis are being increasingly scrutinized, despite their essential role for early translational research. In particular, recent studies have suggested that at the level of the leukocyte transcriptome, murine models of burns, trauma and endotoxemia markedly differ from their human equivalents, and are only weakly similar amongst themselves. We compared the plasma cytokine and leukocyte transcriptome responses between two different low-lethality murine models of polymicrobial intra-abdominal sepsis. Methods: Six to ten week male C57BL/6j mice underwent either the 'gold standard' cecal ligation and puncture (CLP) model of intra-abdominal sepsis or administration of a cecal slurry (CS), where cecal contents are injected intraperitoneally. Surviving mice were euthanized at two hours, one or three days after sepsis. Results: The murine leukocyte transcriptomic response to the CLP and CS models of sepsis was surprisingly dissimilar at two hours, one, and three days after sepsis. The Pearson correlation coefficient for the maximum change in expression for the entire leukocyte transcriptome that changed significantly over time (n = 19,071) was R = 0.54 (R-2 = 0.297). The CS model resulted in greater magnitude of early inflammatory gene expression changes in response to sepsis with associated increased production of inflammatory chemokines and cytokines. Two hours after sepsis, CLP had more significant expression of genes associated with IL-10 signaling pathways, whereas CS had greater expression of genes related to CD28, apoptosis, IL-1 and T-cell receptor signaling. By three days, the changes in gene expression in both sepsis models were returning to baseline in surviving animals. Conclusion: These analyses reveal that the murine blood leukocyte response to sepsis is highly dependent on which model of intra-abdominal sepsis is employed, despite their similar lethality. It may be difficult to extrapolate findings from one murine model to another, let alone to human sepsis.
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页数:10
相关论文
共 34 条
[1]   Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care [J].
Angus, DC ;
Linde-Zwirble, WT ;
Lidicker, J ;
Clermont, G ;
Carcillo, J ;
Pinsky, MR .
CRITICAL CARE MEDICINE, 2001, 29 (07) :1303-1310
[2]  
BARTLETT JG, 1978, ARCH SURG-CHICAGO, V113, P853
[3]   Sir Isaac Newton, sepsis, SIRS, and CARS [J].
Bone, RC .
CRITICAL CARE MEDICINE, 1996, 24 (07) :1125-1128
[4]   Immunosuppression in Patients Who Die of Sepsis and Multiple Organ Failure [J].
Boomer, Jonathan S. ;
To, Kathleen ;
Chang, Kathy C. ;
Takasu, Osamu ;
Osborne, Dale F. ;
Walton, Andrew H. ;
Bricker, Traci L. ;
Jarman, Stephen D., II ;
Kreisel, Daniel ;
Krupnick, Alexander S. ;
Srivastava, Anil ;
Swanson, Paul E. ;
Green, Jonathan M. ;
Hotchkiss, Richard S. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2011, 306 (23) :2594-2605
[5]   Animal models of sepsis: Setting the stage [J].
Buras, JA ;
Holzmann, B ;
Sitkovsky, M .
NATURE REVIEWS DRUG DISCOVERY, 2005, 4 (10) :854-865
[6]   A network-based analysis of systemic inflammation in humans [J].
Calvano, SE ;
Xiao, WZ ;
Richards, DR ;
Felciano, RM ;
Baker, HV ;
Cho, RJ ;
Chen, RO ;
Brownstein, BH ;
Cobb, JP ;
Tschoeke, SK ;
Miller-Graziano, C ;
Moldawer, LL ;
Mindrinos, MN ;
Davis, RW ;
Tompkins, RG ;
Lowry, SF .
NATURE, 2005, 437 (7061) :1032-1037
[7]   A 12-year prospective study of postinjury multiple organ failure - Has anything changed? [J].
Ciesla, DJ ;
Moore, EE ;
Johnson, JL ;
Burch, JM ;
Cothren, CC ;
Sauaia, A .
ARCHIVES OF SURGERY, 2005, 140 (05) :432-439
[8]  
Cuenca AG, 2013, CRIT CARE MED, P5
[9]  
Cuenca Alex G, 2010, Curr Protoc Immunol, VChapter 19, DOI 10.1002/0471142735.im1913s91
[10]   Rodent models of intra-abdominal infection [J].
Deitch, EA .
SHOCK, 2005, 24 :19-23