Skip to main content
SpringerLink
Log in

Chemokines in animal models of inflammation

  • Chapter
Chemokine Biology — Basic Research and Clinical Application

Part of the book series: Progress in Inflammation Research ((PIR))

  • 654 Accesses

Abstract

There is little doubt that animal modeling of various human diseases, disorders, and toxicology has been a staple of both academia and the pharmaceutical industry for decades. While it may be difficult to argue that experimental models, in particular rodent models, of human disease provide an exact mimic of their human counterpart, these experimental systems do provide a mechanism to generate meaningful data in the absence of human specimens. This is especially true in the case of human inflammatory disease where one is unlikely to gain access to tissue samples during the early initiation of a disease, and in the case of chronic disease where continuous, longitudinal samples are nearly impossible to obtain to assess the maintenance stage of chronic disease. Thus, the strategic use of experimental animal systems will continue to be an important tool in assessing both mechanisms of disease and efficacy of drugs which target these diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Rinaldo JER, Rogers RM (1982) Adult respiratory distress syndrome: Changing concepts of lung injury and repair. N Engl J Med 306: 900–909

    Article  PubMed  CAS  Google Scholar 

  2. Strieter RM, Lynch JP, Basha MA, Standiford TJ, Kasahara K, Kunkel SL (1990) Host responses in mediating sepsis and adult respiratory distress syndrome. Seminars in Respir Infect 5: 233–247

    CAS  Google Scholar 

  3. Angele MK, Faist E (2002) Clinical review: Immunodepression in the surgical patient and increased susceptibility to infection. Crit Care 6(4): 298–305

    Article  PubMed  Google Scholar 

  4. Mortelliti MP, Manning HL (2002) Acute respiratory distress syndrome. Am Fam Physician 65(9): 1823–1830

    PubMed  Google Scholar 

  5. Perl TM, Dvorak L, Hwang T, Wenzel RP (1995) Long-term survival and function after suspected gram-negative sepsis. JAMA 274: 338–345

    Article  PubMed  CAS  Google Scholar 

  6. Quartin AA, Schein RM, Kett DH, Peduzzi PN (1997) Magnitude and duration of the effect of sepsis on survival. JAMA 277: 1058–1063

    Article  PubMed  CAS  Google Scholar 

  7. Steinhauser ML, Hogaboam CM, Lukacs NW, Strieter RM, Kunkel SL (1999) Multiple roles for IL-12 in a model of acute septic peritonitis. J Immunol 162: 5437–5433

    PubMed  CAS  Google Scholar 

  8. Donnelly SC, Strieter RM, Kunkel SL, Walz A, Steedman D, Grant IS, Pollok AJ, Carter DC, Haslett C (1994) Chemotactic cytokines in the established adult respiratory distress syndrome and at-risk patients. Chest 105(3 Suppl): 98S–99S

    PubMed  CAS  Google Scholar 

  9. Donnelly SC, Strieter RM, Kunkel SL, Walz A, Robertson CR, Carter DC, Grant IS, Pollok AJ, Haslett C (1993) Interleukin-8 and development of adult respiratory distress syndrome in at-risk patient groups. Lancet Mar 341(8846): 643–647

    Article  PubMed  CAS  Google Scholar 

  10. Bossink AW, Paemen L, Jansen PM, Hack CE, Thijs LG, Van Damme J (1995) Plasma levels of the chemokines monocyte chemotactic proteins-1 and-2 are elevated in human sepsis. Blood 86(10): 3841–3847

    PubMed  CAS  Google Scholar 

  11. Matsukawa A, Hogaboam CM, Lukacs NW, Lincoln PM, Strieter RM, Kunkel SL (1999) Endogenous monocyte chemoattractant protein-1 (MCP-1) protects mice in a model of acute septic: cross-talk between MCP-1 and leukotriene B4. J Immunol 163(11): 6148–6154

    PubMed  CAS  Google Scholar 

  12. Matsukawa A, Hogaboam CM, Lukacs NW, Lincoln PM, Strieter RM, Kunkel SL (2000) Endogenous MCP-1 influences systemic cytokine balance in a murine model of acute septic peritonitis. Exp Mol Pathol 68(2): 77–84

    Article  PubMed  CAS  Google Scholar 

  13. Matsukawa A, Hogaboam C, Lukacs NW, Lincoln P, Evanoff H, Kunkel SL (2000) Pivotal role of the CC chemokine, macrophage derived chemokine, in the innate immune response. J Immunol 164: 5362–5368

    PubMed  CAS  Google Scholar 

  14. Schuh JM, Power CA, Proudfoot AE, Kunkel SL, Lukacs NW, Hogaboam CM (2002) Airway hyperresponsiveness, but not airway remodeling, is attenuated during chronic pulmonary allergic responses to Aspergillus in CCR4-/- mice. FASEB J 16(10): 1313–1315

    PubMed  CAS  Google Scholar 

  15. Chvatchko Y, Hoogewerf AJ, Meyer A, Alouani S, Juillard P, Buser R, Conquet F, Proudfoot AE, Wells TN, Power CA (2000) A key role for CC chemokine receptor 4 in lipopolysaccharide-induced endotoxic shock. J Exp Med 191(10): 1755–1764

    Article  PubMed  CAS  Google Scholar 

  16. Matsukawa A, Hogaboam C, Lukacs NW, Lincoln P, Evanoff H, Kunkel SL (2000) Pivotal role of the CC chemokine, macrophage derived chemokine, in the innate immune response. J Immunol 164: 5362–5368

    PubMed  CAS  Google Scholar 

  17. Romagnani S (1992) Induction of Th1 and Th2 responses: a key role for the natural immune response? Immunol Today 13: 379–381

    Article  PubMed  CAS  Google Scholar 

  18. Chensue SW, Warmington KS, Ruth J, Lincoln PM, Kunkel SL (1994) Cross-regulatory role of interferon-gamma (IFN), IL-4 and IL-10 in schistosome egg granuloma formation: in vivo regulation of Th activity and inflammation. Clin Exp Immunol 98: 395–400

    Article  PubMed  CAS  Google Scholar 

  19. Li YJ, Petrofsky M, Bermudez LE (2002) Mycobacterium tuberculosis uptake by recipient host macrophages is influenced by environmental conditions in the granuloma of the infectious individual and is associated with impaired production of interleukin-12 and tumor necrosis factor alpha. Infect Immun 70: 6223–6230

    Article  PubMed  CAS  Google Scholar 

  20. Fenhalls G, Stevens L, Bezuidenhout J, Amphlett GE, Duncan K, Bardin P, Lukey PT (2002) Distribution of IFN-gamma, IL-4 and TNF-alpha protein and CD8 T cells producing IL-12p40 mRNA in human lung tuberculous granulomas. Immunology 105: 325–335

    Article  PubMed  CAS  Google Scholar 

  21. Jakubzick C, Choi ES, Kunkel SL, Joshi BH, Puri RK, Hogaboam CM (2003) Impact of interleukin-13 responsiveness on the synthetic and proliferative properties of Th1-and Th2-type pulmonary granuloma fibroblasts. Am J Pathol 162: 1475–1486

    PubMed  CAS  Google Scholar 

  22. Mountford AP, Coulson PS, Cheever AW, Sher A, Wilson RA, Wynn TA (1999) Interleukin-12 can directly induce T-helper 1 responses in interferon-gamma (IFN-gamma) receptor-deficient mice, but requires IFN-gamma signalling to downregulate T-helper 2 responses. Immunology 97: 588–594

    Article  PubMed  CAS  Google Scholar 

  23. Lukacs NW, Kunkel SL, Strieter RM, Warmington K, Chensue SW (l993) The role of macrophage inflammatory protein 1 alpha in Schistosoma mansoni egg-induced granulomatous inflammation. J Ex Med 177: 1551–1559

    Article  Google Scholar 

  24. Shang X, Qiu B, Frait KA, Hu JS, Sonstein J, Curtis JL, Lu B, Gerard C, Chensue SW (2000) Chemokine receptor 1 knockout abrogates natural killer cell recruitment and impairs type-1 cytokines in lymphoid tissue during pulmonary granuloma formation. Am J Pathol 157: 2055–2063

    PubMed  CAS  Google Scholar 

  25. Gao JL, Wynn TA, Chang Y, Lee EJ, Broxmeyer HE, Cooper S, Tiffany HL, Westphal H, Kwon-Chung J, Murphy PM (1997) Impaired host defense, hematopoiesis, granulomatous inflammation and type 1-type 2 cytokine balance in mice lacking CC chemokine receptor 1. J Exp Med 185: 1959–1968

    Article  PubMed  CAS  Google Scholar 

  26. Warmington KS, Boring L, Ruth JH, Sonstein J, Hogaboam CM, Curtis JL, Kunkel SL, Charo IR, Chensue SW (1999) Effect of C-C chemokine receptor 2 (CCR2) knockout on type-2 (schistosomal antigen-elicited) pulmonary granuloma formation: analysis of cellular recruitment and cytokine responses. Am J Pathol 154: 1407–1416

    PubMed  CAS  Google Scholar 

  27. Sekiya T, Yamada H, Yamaguchi M, Yamamoto K, Ishii A, Yoshie O, Sano Y, Morita A, Matsushima K, Hirai K (2002) Increased levels of a TH2-type CC chemokine thymus and activation-regulated chemokine (TARC) in serum and induced sputum of asthmatics. Allergy 57: 173–177

    Article  PubMed  CAS  Google Scholar 

  28. Nouri-Aria KT, Wilson D, Francis JN, Jopling LA, Jacobson MR, Hodge MR, Andrew DP, Till SJ, Varga EM, Williams TJ et al (2002) CCR4 in human allergen-induced late responses in the skin and lung. Eur J Immunol 32: 1933–1938

    Article  PubMed  CAS  Google Scholar 

  29. Hirata H, Arima M, Cheng G, Honda K, Fukushima F, Yoshida N, Eda F, Fukuda T (2003) Production of TARC and MDC by naive T cells in asthmatic patients. J Clin Immunol 23: 34–45

    Article  PubMed  CAS  Google Scholar 

  30. Leung TF, Wong CK, Lam CW, Li AM, Ip WK, Wong GW, Fok TF (2003) Plasma TARC concentration may be a useful marker for asthmatic exacerbation in children. Eur Respir J 21: 616–620

    Article  PubMed  CAS  Google Scholar 

  31. Panina-Bordignon P, Papi A, Mariani M, Di Lucia P, Casoni G, Bellettato C, Buonsanti C, Miotto D, Mapp C, Villa A et al. (2001) The C-C chemokine receptors CCR4 and CCR8 identify airway T cells of allergen-challenged atopic asthmatics. J Clin Invest 107: 1357–1364

    PubMed  CAS  Google Scholar 

  32. Alferink J, Lieberam I, Reindl W, Behrens A, Weiss S, Huser N, Gerauer K, Ross R, Reske-Kunz AB, Ahmad-Nejaad P et al (2003) Compartmentalized production of CCL17 in vivo: strong inducibility in peripheral dendritic cells contrasts selective absence from the spleen. J Exp Med 197: 585–599

    Article  PubMed  CAS  Google Scholar 

  33. Rothenberg ME, MacLean JA, Pearlman E, Luster AD, and Leder P (1997) Targeted disruption of the chemokine eotaxin partially reduces antigen-induced tissue eosinophilia. J Exp Med 185: 785

    Article  PubMed  CAS  Google Scholar 

  34. Humbles AA, B Lu, Friend DS, Okinaga S, Lora, Al-Garawi, Martin TR, Gerard NP, Gerard C (2002) The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness. Proc Natl Acad Sci USA 99: 1479

    Article  PubMed  CAS  Google Scholar 

  35. Sallusto F, Mackay CR, Lanzavecchia A (2000) The role of chemokine receptors in primary, effector, and memory immune responses. Annu Rev Immunol 18: 593

    Article  PubMed  CAS  Google Scholar 

  36. Chung CD, Kuo F, Kumer J, Motani AS, Lawrence CE, Henderson WR Jr, Venkataraman C (2003) CCR8 is not essential for the development of inflammation in a mouse model of allergic airway disease. J Immunol 170: 581

    PubMed  CAS  Google Scholar 

  37. Borchers MT, Ansay T, DeSalle R, Daugherty BL, Shen H, Metzger M, Lee NA, Lee JJ (2002)In vitro assessment of chemokine receptor-ligand interactions mediating mouse eosinophil migration. J Leukoc Biol 71: 1033

    PubMed  CAS  Google Scholar 

  38. Lukacs NW, Prosser D, Wiekowski M, Lira SA, Cook DN (2001) Requirement for the chemokine receptor CCR6 in allergic pulmonary inflammation. J Exp Med 194: 551

    Article  PubMed  CAS  Google Scholar 

  39. Lundy SK, Lira SA, Smit JJ, Cook DN, Berlin AA, Lukacs NW (2005) Attenuation of allergen-induced responses in CCR6-/-mice is dependent upon altered pulmonary T lymphocyte activation. J Immunol 174: 2054

    PubMed  CAS  Google Scholar 

  40. Godessart N, Kunkel SL (2001) Chemokines in autoimmune disease. Curr Opin Immunol 13: 670–675

    Article  PubMed  CAS  Google Scholar 

  41. Kunkel SL, Godessart N (2002) Chemokines in autoimmunity: from pathology to therapeutics. Autoimmun Rev 1: 313–320

    Article  PubMed  CAS  Google Scholar 

  42. Koch AE (2005) Chemokines and their receptors: future targets? Arthritis Rheum 52: 710–721

    Article  PubMed  Google Scholar 

  43. Nissinen R, Leirisalo-Repo M, Peltomaa R, Palosuo T, Vaarala O (2004) Cytokine and chemokine receptor profile of peripheral blood mononuclear cells during treatment with infliximab in patients with active rheumatoid arthritis. Ann Rheum Dis 63: 681–687

    Article  PubMed  CAS  Google Scholar 

  44. Ho CY, Wong CK, Li EK, Tam LS, Lam CW (2003) Suppressive effect of combination treatment of leflunomide and methotrexate on chemokine expression in patients with rheumatoid arthritis. Clin Exp Immunol Jul 133(1): 132–138

    Article  PubMed  CAS  Google Scholar 

  45. Volin MV, Campbell PL, Connors MA, Woodruff DC, Koch AE (2002) The effect of sulfasalazine on rheumatoid arthritic synovial tissue chemokine production. Exp Mol Pathol 73: 84–92

    Article  PubMed  CAS  Google Scholar 

  46. Ellimngsen T, Buus A, Syengarrd-Petersen K (2001) Plasma monocyte chemoattractant protein 1 is a marker for joint inflammation in rheumatoid arthritis. J Rheumatol 28: 41–46

    Google Scholar 

  47. Boiardi L, Macchioni P, Meliconi R, Pulsatelli L, Facchini A, Salvarani C (1999) Relationship between serum RANTES levels and radiological progression in rheumatoid arthritis patients treated with methotrexate. Clin Exp Rheumatol 17: 419–425

    PubMed  CAS  Google Scholar 

  48. Bendele A (2001) Animal models of rheumatoid arthritis. J Musculoskelet Neuronal Interact 1: 377–385

    PubMed  CAS  Google Scholar 

  49. Kasama T, Strieter RM, Lukacs NW, Lincoln PM, Burdick MD, Kunkel SL (1995) Interleukin 10 expression and chemokine regulation during the evolution of murine type II collagen-induced arthritis. J Clin Invest 95: 2868–2876

    Article  PubMed  CAS  Google Scholar 

  50. Nanki T, Urasaki Y, Nishimura M, Muramot K, Kubota T, Miyasaka N (2004) Inhibition of fractalkine ameliorates murine collagen-induced arthritis. J Immunol 173: 7010–7016

    PubMed  CAS  Google Scholar 

  51. Zheng B, Ozen Z, Zhang X, De Silva S, Marinova E, Guo L, Wansley D, Huston DP, West MR, Han S (2005) CXCL13 neutralization reduces the severity of collageninduced arthritis. Arthritis Rheum 52: 620–626

    Article  PubMed  CAS  Google Scholar 

  52. Saeki T, Naya A (2003) CCR1 chemokine receptor antagonist. Current Pharm Design 9: 1201–1208

    Article  CAS  Google Scholar 

  53. Matthys P, Hatse S, Vermeire K, Wuyts A, Bridger G, Henson GW, De Clercq E, Billiau A, Schols D (2001) AMD3100, a potent and specific antagonist of the stromal cellderived factor-1 chemokine receptor CXCR4, inhibits autoimmune joint inflammation in IFN-gamma receptor-deficient mice. J Immunol 167(8): 4686–4692

    PubMed  CAS  Google Scholar 

  54. Yang YF, Mukai T, Gao P, Yamaguchi N, Ono S, Iwaki H, Obika S, Imanishi T, Tsujimura T, Hamaoka T et al. (2002) A non-peptide CCR5 antagonist inhibits collageninduced arthritis by modulating T cell migration without affecting anti-collagen T cell responses. Eur J Immunol 32: 2124–2132

    Article  PubMed  CAS  Google Scholar 

  55. Plater-Zyberk C, Hoogewerf AJ, Proudfoot AE, Power CA, Wells TN (1997) Effect of a CC chemokine receptor antagonist on collagen induced arthritis in DBA/1 mice. Immunol Lett 57(1–3): 117–120

    Article  PubMed  CAS  Google Scholar 

  56. Quinones MP, Ahuja SK, Jimenez F, Schaefer J, Garavito E, Rao A, Chenaux G, Reddick RL, Kuziel WA, Ahuja SS (2004) Experimental arthritis in CC Chemokine receptor 2-null mice closely mimics severe human rheumatoid arthritis. J Clin Invest 113: 856–866

    Article  PubMed  CAS  Google Scholar 

  57. Bruhl H, Cihak J, Schneider MA, Plachy J, Rupp T, Wenzel I, Shakarami M, Milz S, Ellwart JW, Stangassinger M et al (2004). Dual role of CCR2 during initiation and progression of collagen-induced arthritis: evidence for regulatory activity of CCR2+ T cells. J Immunol 172: 890–898

    PubMed  Google Scholar 

  58. Gladue RP, Zwillich SH, Clucas AT, Brown MF (2004) CCR1 antagonists for the treatment of autoimmune diseases. Curr Opin Invest Drugs 5: 499–504

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, The University of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-0602, USA

    Steven L. Kunkel, Cory Hogaboam, Stephen W. Chensue & Nicholas Lukacs

  2. The University of Michigan Medical and Veterans Administration Hospital, Ann Arbor, MI, USA

    Stephen W. Chensue

  3. Almirall Research Center, Sant Feliu de Llobregat, Spain

    Nuria Godessart

Authors
  1. Steven L. Kunkel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nuria Godessart
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cory Hogaboam
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stephen W. Chensue
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nicholas Lukacs
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Lilly Corporate Center, Cancer Inflammation and Cell Survival Eli Lilly and Company, Indianapolis, IN, 46285, USA

    Kuldeep Neote

  2. NitroMed, Inc., 12 Oak Park Drive, Bedford, MA, 01730, USA

    Gordon L. Letts

  3. Theodor Koch Institute, University of Bern, Freiestrasse 1, 3012, Bern, Switzerland

    Bernhard Moser

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Birkhäuser Verlag Basel/Switzerland

About this chapter

Cite this chapter

Kunkel, S.L., Godessart, N., Hogaboam, C., Chensue, S.W., Lukacs, N. (2007). Chemokines in animal models of inflammation. In: Neote, K., Letts, G.L., Moser, B. (eds) Chemokine Biology — Basic Research and Clinical Application. Progress in Inflammation Research. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-7437-2_1

Download citation

Publish with us

Policies and ethics

Search

Navigation