Modeling sepsis in the laboratory: merging sound science with animal well-being.

Jean A Nemzek, Kelly M S Hugunin, Mark R Opp
Author Information
  1. Jean A Nemzek: Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI, USA. jnemzek@umich.edu

Abstract

Despite impressive advances in biomedical research, few noteworthy breakthroughs have been made in the treatment of sepsis during the past several decades. This stalemate is primarily due to the intricate and heterogenic nature of the systemic immune responses characterized as the sepsis syndrome. In general, such complexity must be approached with in vivo models. Several animal models have been described, suggesting that none adequately address all of the pressing needs in sepsis research. The most clinically applicable models involve a localized infection, such as surgically induced polymicrobial sepsis, that gradually propagates a systemic immune response. Because relevant models must mimic a severe and chronic syndrome, animal well-being is often a concern in sepsis research. A balance between the needs of sepsis research and animal welfare can only be achieved through knowledge of the strengths and weaknesses of and alternatives to in vivo sepsis models.

References

  1. Shock. 2004 Jan;21(1):17-25 [PMID: 14676679]
  2. J Surg Res. 1983 Feb;34(2):151-8 [PMID: 6337304]
  3. J Immunol. 2002 Mar 1;168(5):2493-500 [PMID: 11859143]
  4. Shock. 2005 Dec;24 Suppl 1:58-63 [PMID: 16374374]
  5. Circ Shock. 1985;17(4):273-84 [PMID: 4092342]
  6. Immunopharmacology. 2000 Jul 20;48(2):145-56 [PMID: 10936512]
  7. Shock. 2007 Jul;28(1):59-64 [PMID: 17483746]
  8. Shock. 2002 Nov;18(5):445-9 [PMID: 12412624]
  9. Surgery. 1996 Aug;120(2):290-6 [PMID: 8751595]
  10. Int J Exp Pathol. 1992 Feb;73(1):95-8 [PMID: 1576081]
  11. Shock. 2004 Oct;22(4):364-8 [PMID: 15377893]
  12. Shock. 1998 Aug;10(2):110-7 [PMID: 9721977]
  13. World J Gastroenterol. 2006 Dec 7;12(45):7350-4 [PMID: 17143955]
  14. Shock. 2004 Aug;22(2):189; author reply 189-90 [PMID: 15257095]
  15. Crit Care Med. 2004 May;32(5 Suppl):S219-22 [PMID: 15118521]
  16. J Surg Res. 1984 May;36(5):516-25 [PMID: 6374288]
  17. Crit Care Med. 2001 Jul;29(7):1303-10 [PMID: 11445675]
  18. Immunol Res. 2001;24(3):273-87 [PMID: 11817325]
  19. Shock. 2000 Aug;14(2):81-90 [PMID: 10947147]
  20. J Immunol. 2001 Jun 1;166(11):6952-63 [PMID: 11359857]
  21. J Invest Surg. 2001 Jul-Aug;14(4):195-212 [PMID: 11680530]
  22. J Trauma. 1981 Mar;21(3):215-20 [PMID: 6783763]
  23. Shock. 2005 Dec;24 Suppl 1:12-8 [PMID: 16374367]
  24. Minerva Anestesiol. 2005 Jan-Feb;71(1-2):39-52 [PMID: 15711505]
  25. N Engl J Med. 2001 Mar 8;344(10):699-709 [PMID: 11236773]
  26. Am J Physiol. 1994 Jan;266(1 Pt 2):R125-35 [PMID: 8304533]
  27. Shock. 2002 Oct;18(4):342-7 [PMID: 12392278]
  28. Infect Immun. 1999 Mar;67(3):1521-5 [PMID: 10024605]
  29. Am J Physiol. 1988 Mar;254(3 Pt 2):H558-69 [PMID: 3279822]
  30. Anesthesiology. 2004 Oct;101(4):902-11 [PMID: 15448523]
  31. Am J Physiol Regul Integr Comp Physiol. 2006 Mar;290(3):R685-93 [PMID: 16269570]
  32. N Engl J Med. 2003 Jan 9;348(2):138-50 [PMID: 12519925]
  33. Ann Surg. 1968 May;167(5):630-50 [PMID: 4869050]
  34. JAMA. 1995 Mar 22-29;273(12):934-41 [PMID: 7884952]
  35. Infect Immun. 1998 May;66(5):2300-9 [PMID: 9573121]
  36. Crit Care Med. 1999 Apr;27(4):733-40 [PMID: 10321662]
  37. Crit Care Med. 1997 Jul;25(7):1115-24 [PMID: 9233735]
  38. Shock. 2005 Dec;24 Suppl 1:52-7 [PMID: 16374373]
  39. Eur Surg Res. 2003 Nov-Dec;35(6):486-91 [PMID: 14593232]
  40. J Immunol. 2002 Sep 15;169(6):2823-7 [PMID: 12218091]
  41. Brain Behav Immun. 2005 Jan;19(1):40-51 [PMID: 15581737]
  42. Shock. 2004 Apr;21(4):329-35 [PMID: 15179133]
  43. Br J Surg. 2001 Jan;88(1):22-30 [PMID: 11136305]
  44. Shock. 1999 Aug;12(2):118-26 [PMID: 10446892]
  45. Crit Care Med. 1993 Feb;21(2):191-5 [PMID: 8428468]
  46. Surgery. 1980 Jul;88(1):41-7 [PMID: 6992321]
  47. Crit Care Med. 2005 Jan;33(1):161-7 [PMID: 15644664]
  48. Shock. 2000 Feb;13(2):100-9 [PMID: 10670839]
  49. Immunology. 2003 Jul;109(3):426-31 [PMID: 12807489]
  50. Pain. 2004 Jul;110(1-2):385-92 [PMID: 15275790]
  51. Crit Care Med. 2003 Aug;31(8):2096-101 [PMID: 12973165]
  52. Contemp Top Lab Anim Sci. 2003 Mar;42(2):39-42 [PMID: 19757624]
  53. Contemp Top Lab Anim Sci. 2004 Sep;43(5):13-8 [PMID: 15461434]
  54. J Infect Dis. 1997 Jul;176(1):183-8 [PMID: 9207365]
  55. Surgery. 1979 Feb;85(2):205-11 [PMID: 419461]
  56. JAMA. 1994 Jun 15;271(23):1836-43 [PMID: 8196140]
  57. Shock. 2002 Jun;17(6):463-7 [PMID: 12069181]
  58. Immunol Res. 2006;36(1-3):237-45 [PMID: 17337784]
  59. J Surg Res. 1980 Aug;29(2):189-201 [PMID: 6997619]
  60. Crit Care Med. 2004 Nov;32(11 Suppl):S554-61 [PMID: 15542964]
  61. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5939-43 [PMID: 293694]
  62. Circ Shock. 1989 Dec;29(4):279-90 [PMID: 2598414]
  63. Cytokine. 2004 Feb 7;25(3):110-8 [PMID: 14698137]
  64. Am J Ther. 2004 Sep-Oct;11(5):354-65 [PMID: 15356431]
  65. N Engl J Med. 1987 Sep 10;317(11):653-8 [PMID: 3306374]
  66. Infect Immun. 1999 Dec;67(12):6603-10 [PMID: 10569781]
  67. J Clin Invest. 2003 Aug;112(4):460-7 [PMID: 12925683]
  68. Palliat Med. 2006;20 Suppl 1:s9-15 [PMID: 16764216]
  69. J Immunol. 1992 Mar 15;148(6):1890-7 [PMID: 1541827]
  70. Surg Gynecol Obstet. 1975 Jul;141(1):27-34 [PMID: 1154209]
  71. Clin Diagn Lab Immunol. 2005 Jan;12(1):60-7 [PMID: 15642986]
  72. Lab Anim. 1998 Jul;32(3):260-9 [PMID: 9718473]
  73. Shock. 2000 Aug;14(2):157-62 [PMID: 10947160]
  74. J Immunol. 1996 Dec 15;157(12):5748-54 [PMID: 8955229]
  75. J Immunol. 2006 Aug 1;177(3):1967-74 [PMID: 16849510]
  76. Crit Care Med. 1992 Jun;20(6):724-6 [PMID: 1597021]
  77. J Intern Med. 2006 Feb;259(2):138-54 [PMID: 16420543]
  78. Anesthesiology. 1985 Sep;63(3):267-73 [PMID: 4025889]
  79. Shock. 2005 Jan;23(1):11-7 [PMID: 15614125]
  80. Circ Shock. 1987;21(3):207-16 [PMID: 3552282]
  81. J Surg Res. 1990 Aug;49(2):186-96 [PMID: 2199735]
  82. Crit Care Med. 1996 May;24(5):733-42 [PMID: 8706447]
  83. Am J Physiol Lung Cell Mol Physiol. 2000 Mar;278(3):L512-20 [PMID: 10710523]
  84. Mech Ageing Dev. 2003 Dec;124(10-12):1047-58 [PMID: 14659593]
  85. Nat Rev Drug Discov. 2005 Oct;4(10):854-65 [PMID: 16224456]
  86. Shock. 2000 Feb;13(2):110-6 [PMID: 10670840]
  87. Ann Surg. 1992 Aug;216(2):117-34 [PMID: 1503516]
  88. J Clin Invest. 1986 Jul;78(1):259-70 [PMID: 3722379]
  89. Infect Immun. 1993 Jul;61(7):2741-7 [PMID: 8514375]
  90. Shock. 2004 Jun;21(6):505-11 [PMID: 15167678]
  91. Shock. 1998 Jan;9(1):1-11 [PMID: 9466467]
  92. Shock. 1996 Dec;6(6):442-51 [PMID: 8961395]
  93. Eur J Immunol. 2004 Dec;34(12):3664-73 [PMID: 15517610]
  94. Anesth Analg. 2006 Mar;102(3):876-81 [PMID: 16492844]
  95. ILAR J. 2000;41(2):72-9 [PMID: 11406700]
  96. Lab Anim Sci. 1999 Oct;49(5):545-50 [PMID: 10551457]
  97. Surgery. 1983 Aug;94(2):331-5 [PMID: 6879447]

Grants

  1. HL080972/NHLBI NIH HHS
  2. R01 HL080972/NHLBI NIH HHS
  3. P01 GM067189-030003/NIGMS NIH HHS
  4. K08 GM065486/NIGMS NIH HHS
  5. GM65486/NIGMS NIH HHS
  6. GM067189/NIGMS NIH HHS
  7. R01 HL080972-04/NHLBI NIH HHS
  8. P01 GM067189/NIGMS NIH HHS

MeSH Term

Animal Welfare
Animals
Disease Models, Animal
Drug Evaluation, Preclinical
Sepsis

Word Cloud

Created with Highcharts 10.0.0sepsismodelsresearchanimalsystemicimmunesyndromemustvivoneedswell-beingDespiteimpressiveadvancesbiomedicalnoteworthybreakthroughsmadetreatmentpastseveraldecadesstalemateprimarilydueintricateheterogenicnatureresponsescharacterizedgeneralcomplexityapproachedSeveraldescribedsuggestingnoneadequatelyaddresspressingclinicallyapplicableinvolvelocalizedinfectionsurgicallyinducedpolymicrobialgraduallypropagatesresponserelevantmimicseverechronicoftenconcernbalancewelfarecanachievedknowledgestrengthsweaknessesalternativesModelinglaboratory:mergingsoundscience

Similar Articles

Cited By