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Acute and Chronic Models of Allergic Contact Dermatitis: Advantages and Limitations

  • T. M. Zollner
  • F. H. Igney
  • K. Asadullah
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 50)

15.6 Conclusion

Basic immunological research has not only provided a deeper insight into the pathophysiology of ACD but has also generated a plethora of appealing animal models for both acute and chronic ACD. Some of the more established models are already extensively characterized and have proven to be T cell-dependent with an involvement of Th1 and Tc1 cells. They display at least some of the classical histological hallmarks of human ACD, and responses to experimental therapies in rodents do to a large extent reflect the human situation. However, the established models are mostly acute, self-limited inflammation models. More recent developments such as mice overexpressing costimulatory or angiogenic molecules need further characterization. Gene and protein expression profiling would allow comparisons of expression profiles in human disease with those obtained from different animal models. More systematic investigations regarding the effects of well established effective therapeutic approaches in humans and in model situations compared to drugs effective only in contact dermatitis models, not in humans would be desirable. In the future, this may help to select relevant models for specific needs such as functional target validation and compound characterization and may finally provide the desired, more predictive in vivo models.

Keywords

Contact Dermatitis Allergic Contact Dermatitis Allergen Challenge Mometasone Furoate Contact Hypersensitivity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Abe Y, Sugisaki K, Dannenberg AMJ (1996) Rabbit vascular endothelial adhesion molecules: ELAM-1 is most elevated in acute inflammation, whereas VCAM-1 and ICAM-1 predominate in chronic inflammation. J Leukoc Biol 60:692–703PubMedGoogle Scholar
  2. Achten G, Bourlond A, Haven E, Lapiere CM, Pierard J, Reynaers H (1973) Bufexamac cream and ointment for the treatment of various dermatoses. Dermatologica 146:1–7PubMedGoogle Scholar
  3. Asadullah K, Sterry W, Stephanek K, Jasulaitis D, Leupold M, Audring H, Volk H-D, Docke W-D (1998) IL-10 is a key cytokine in psoriasis. Proof of principle by IL-10 therapy: A new therapeutic approach. J Clin Invest 101:783–794PubMedCrossRefGoogle Scholar
  4. Askenase PW (2001) Yes T cells, but three different T cells (α\, γδ and NK T cells), and also B-1 cells mediate contact sensitivity. Clin Exp Immunol 125:345–350PubMedCrossRefGoogle Scholar
  5. Betts CJ, Dearman RJ, Flanagan BF, Kimber I (2002) Temporal changes in cytokine gene expression profiles induced in mice by trimellitic anhydride. Toxicology Letters 136:121–132PubMedCrossRefGoogle Scholar
  6. Biedermann T, Kneilling M, Mailhammer R, Maier K, Sander CA, Kollias G, Kunkel SL, Hultner L, Rocken M (2000) Mast cells control neutrophil recruitment during T cell-mediated delayed-type hypersensitivity reactions through tumor necrosis factor and macrophage inflammatory protein 2. J Exp Med 192:1441–1452PubMedCrossRefGoogle Scholar
  7. Bouloc A, Cavani A, Katz SI (1998) Contact hypersensitivity in MHC class II-deficient mice depends on CD8 T lymphocytes primed by immunostimulating Langerhans cells. J Invest Dermatol 111:44–49PubMedCrossRefGoogle Scholar
  8. Boyera N, Cavey D, Bouclier M, Burg G, Rossio P, Hensby C (1992) Repeated application of dinitrochlorobenzene to the ears of sensitized guinea pigs: a preliminary characterization of a potential new animal model for contact eczema in humans. Skin Pharmacol 5:184–188PubMedCrossRefGoogle Scholar
  9. Brazzini B, Pimpinelli N (2002) New and established topical corticosteroids in dermatology: clinical pharmacology and therapeutic use. Am J Clin Dermatol 3:47–58PubMedCrossRefGoogle Scholar
  10. Brown LF, Olbricht SM, Berse B, Jackman RW, Matsueda G, Tognazzi KA, Manseau EJ, Dvorak HF, Van de Water L (1995) Overexpression of vascular permeability factor (VPF/VEGF) and its endothelial cell receptors in delayed hypersensitivity skin reactions. J Immunol 154(6):2801–2807PubMedGoogle Scholar
  11. Carroll JM, Crompton T, Seery JP, Watt FM (1997) Transgenic mice expressing IFN-γ in the epidermis have eczema, hair hypopigmentation, and hair loss. J Invest Dermatol 108:412–422PubMedCrossRefGoogle Scholar
  12. Christiansen JV, Gadborg E, Kleiter I, Ludvigsen K, Meier CH, Norholm A, Reiter H, Reymann F, Raaschou-Nielsen W, Sondergaard M, Unna P, Wehnert R (1977) Efficacy of bufexamac (NFN) cream in skin diseases. A double-blind multicentre trial. Dermatologica 1977; 154(3):177–184PubMedCrossRefGoogle Scholar
  13. Dearman RJ, Basketter DA, Kimber I (1996) Characterization of chemical allergens as a function of divergent cytokine secretion profiles induced in mice. Toxicology and Applied Pharmacology 138:308–316PubMedCrossRefGoogle Scholar
  14. Dearman RJ, Warbrick EV, Skinner R, Kimber I (2002) Cytokine fingerprinting of chemical allergens: species comparisons and statistical analyses. Food and Chemical Toxicology 40:1881–1892PubMedCrossRefGoogle Scholar
  15. Detmar M, Brown LF, Schon MP, Elicker BM, Velasco P, Richard L, Fuku-mura D, Monsky W, Claffey KP, Jain RK (1998) Increased microvascular density and enhanced leukocyte rolling and adhesion in the skin of VEGF transgenic mice. J Invest Dermatol 111:1–6PubMedCrossRefGoogle Scholar
  16. Dvorak AM, Mihm MCJ, Dvorak HF (1976) Morphology of delayed-type hypersensitivity reactions in man. II. Ultrastructural alterations affecting the microvasculature and the tissue mast cells. Lab Invest 34:179–191PubMedGoogle Scholar
  17. Ekerdt R, Buchmann B, Frohlich W, Giesen C, Heindl J, Skuballa W (1991) The role of leukotriene B4 as an inflammatory mediator in skin and the functional characterisation of LTB4 receptor antagonists. Adv Prostaglandin Thromboxane Leukot Res 21B:565–568PubMedGoogle Scholar
  18. Fujii Y, Takeuchi H, Tanaka K, Sakuma S, Ohkubo Y, Mutoh S (2002) Effects of FK506 (tacrolimus hydrate) on chronic oxazolone-induced dermatitis in rats. European Journal of Pharmacology 456:115–121PubMedCrossRefGoogle Scholar
  19. Fuller BW, Nishimura T, Noelle RJ (2002) The selective triggering of CD40 on keratinocytes in vivo enhances cell-mediated immunity. Eur J Immunol 32:895–902PubMedCrossRefGoogle Scholar
  20. Garrigue JL, Nicolas JF, Demidem A, Bour H, Viac G, Thivolet J, Schmitt D (1993) Contact sensitivity in mice: Differential effect of vitamin D3 derivative (calcipotriol) and corticosteroids. Clin Immun and Immunopath 67:137–142CrossRefGoogle Scholar
  21. Girolomoni G, Sebastiani S, Albanesi C, Cavani A (2001) T-cell subpopulations in the development of atopic and contact allergy. Current Opinion in Immunology 13:733–737PubMedCrossRefGoogle Scholar
  22. Gocinski BL, Tigelaar RE (1990) Roles of CD4+ and CD8+ T cells in murine contact sensitivity revealed by in vivo monoclonal antibody depletion. J Immunol 144:4121–4128PubMedGoogle Scholar
  23. Gorbachev AV, Fairchild RL (2001) Induction and regulation of T-cell priming for contact hypersensitivity. Crit Rev Immunol 21:451–472PubMedGoogle Scholar
  24. Gottlieb SL, Gilleaudeau P, Johnson R, Estes L, Woodworm TG, Gottlieb AB, Krueger JG (1995) Response of psoriasis to a lymphocyte-selective toxin (DAB389IL-2) suggests a primary immune, but not keratinocyte, pathogenic basis. Nat Med 1:442–447PubMedCrossRefGoogle Scholar
  25. Grabbe S, Schwarz T (1998) Immunoregulatory mechanisms involved in elicitation of allergic contact hypersensitivity. Immunology Today 19:37–44PubMedCrossRefGoogle Scholar
  26. Harada A, Mukaida N, Matsushima K (1996) Interleukin 8 as a novel target for intervention therapy in acute inflammatory diseases. Mol Med Today 2:482–489PubMedCrossRefGoogle Scholar
  27. Higgins EM, McLelland J, Friedmann PS, Matthews JN, Shuster S (1991) Oral cyclosporin inhibits the expression of contact hypersensitivity in man. J Dermatol Sci 2:79–83PubMedCrossRefGoogle Scholar
  28. Kalish R, Askenase P (1999) Molecular mechanisms of CD8+ T cell-mediated delayed hypersensitivity: Implications for allergies, asthma, and autoimmunity. J Allergy and Clin Immunol 103:192–199CrossRefGoogle Scholar
  29. Kapp VJ, Koch H, Casals-Stenzel J, Topert M, Gerhards E (1976) Studies on the pharmacology of 6alpha,9-difluoro-11β-hydroxy-16α-methyl-21-valer-yloxy-1,4-pregnadiene-3,20-dione (diflucortolon valerate). Arzneimittelforschung 26:1463–1475PubMedGoogle Scholar
  30. Kimber I, Dearman RJ (2002) Allergic contact dermatitis: The cellular effectors. Contact Dermatitis 46:1–5PubMedCrossRefGoogle Scholar
  31. Kitagaki H, Fujisawa S, Watanabe K, Hayakawa K, Shiohara T (1995) Immediate-type hypersensitivity response followed by a late reaction is induced by repeated epicutaneous application of contact sensitizing agents in mice. J Invest Dermatol 105:749–755PubMedCrossRefGoogle Scholar
  32. Kitagaki H, Kimishima M, Teraki Y, Hayakawa J, Hayakawa K, Fujisawa S, Shiohara T (1999) Distinct in vivo and in vitro cytokine profiles of draining lymph node cells in acute and chronic phases of contact hypersensitivity: Importance of a Type 2 cytokine-rich cutaneous milieu for the development of an early-type response in the chronic phase. J Immunol 163:1265–1273PubMedGoogle Scholar
  33. Kitagaki H, Ono N, Hayakawa K, Kitazawa T, Watanabe K, Shiohara T (1997) Repeated elicitation of contact hypersensitivity induces a shift in cutaneous cytokine milieu from a T helper cell type 1 to a T helper cell type 2 profile. J Immunol 159:2484–2491PubMedGoogle Scholar
  34. Lange-Asschenfeldt B, Weninger W, Velasco P, Kyriakides TR, von Andrian UH, Bornstein P, Detmar M (2002) Increased and prolonged inflammation and angiogenesis in delayed-type hypersensitivity reactions elicited in the skin of thrombospondin-2-deficient mice. Blood 99:538–545PubMedCrossRefGoogle Scholar
  35. Larsen CG, Thomsen MK, Gesser B, Thomsen PD, Deleuran BW, Nowak J, Skodt V, Thomsen HK, Deleuran M, Thestrup-Pedersen K (1995) The delayed-type hypersensitivity reaction is dependent on IL-8. Inhibition of a tuberculin skin reaction by an anti-IL-8 monoclonal antibody. J Immunol 155:2151–2157PubMedGoogle Scholar
  36. Lauerma AI, Maibach HI, Granlund H, Erkko P, Kartamaa M, Stubb S (1992) Inhibition of contact allergy reactions by topical FK506. Lancet 340:556PubMedCrossRefGoogle Scholar
  37. Mehling A, Grabbe S, Voskort M, Schwarz T, Luger TA, Beissert S (2000) Mycophenolate mofetil impairs the maturation and function of murine dendritic cells. J Immunol 165:2374–2381PubMedGoogle Scholar
  38. Mehling A, Loser K, Varga G, Metze D, Luger TA, Schwarz T, Grabbe S, Beissert S (2001) Overexpression of CD40 ligand in murine epidermis results in chronic skin inflammation and systemic autoimmunity. J Exp Med 194:615–628PubMedCrossRefGoogle Scholar
  39. Meingassner JG, Fahrngruber H, Bavandi A (2003) Pimecrolimus inhibits the elicitation phase but does not suppress the sensitization phase in murine contact hypersensitivity, in contrast to tacrolimus and cyclosporine A. J Invest Dermatol 121:77–80PubMedCrossRefGoogle Scholar
  40. Meingassner JG, Grassberger M, Fahrngruber H, Moore HD, Schuurman H, Stutz A (1997) A novel anti-inflammatory drug, SDZ ASM 981, for the topical and oral treatment of skin diseases: in vivo pharmacology. Br J Dermatol 137:568–576PubMedCrossRefGoogle Scholar
  41. Mizgerd JP, Bullard DC, Hicks MJ, Beaudet AL, Doerschuk CM (1999) Chronic inflammatory disease alters adhesion molecule requirements for acute neutrophil emigration in mouse skin. J Immunol 162:5444–5448PubMedGoogle Scholar
  42. Morrison JG, Schulz EJ (1978) Treatment of eczema with cyclophosphamide and azathioprine. Br J Dermatol 98:203–207PubMedCrossRefGoogle Scholar
  43. Nagai H, Matsuo A, Hiyama H, Inagaki N, Kawada K (1997) Immunoglobulin E production in mice by means of contact sensitization with a simple chemical, hapten. J Allergy Clin Immunol 100:S39–44PubMedCrossRefGoogle Scholar
  44. Nasir A, Ferbel B, Salminen W, Barth RK, Gaspari AA (1994) Exaggerated and persistent cutaneous delayed-type hypersensitivity in transgenic mice whose epidermal keratinocytes constitutively express B7-1 antigen. J Clin Invest 94:892–898PubMedCrossRefGoogle Scholar
  45. Natsuaki M, Yano N, Yamaya K, Kitano Y (2000) Immediate contact hypersensitivity induced by repeated hapten challenge in mice. Contact Dermatitis 43:267–272PubMedCrossRefGoogle Scholar
  46. Pickenacker A, Luger TA, Schwarz T (1998) Dyshidrotic eczema treated with mycophenolate mofetil. Arch Dermatol 134:378–379PubMedCrossRefGoogle Scholar
  47. Prinz J, Braun-Falco O, Meurer M, Daddona P, Reiter C, Rieber P, Riethmuller G (1991) Chimaeric CD4 monoclonal antibody in treatment of generalised pustular psoriasis. Lancet 338:320–321PubMedCrossRefGoogle Scholar
  48. Pullerits T, Lundin S, Dahlgren U, Telemo E, Hanson LA, Lotvall J (1999) An IL-2-toxin, DAB389IL-2, inhibits delayed-type hypersensitivity but enhances IgE antibody production. J Allergy Clin Immunol 103(5 Pt 1): 843–849PubMedCrossRefGoogle Scholar
  49. Queille-Roussel C, Duteil L, Padilla JM, Poncet M, Czernielewski J (1990) Objective assessment of topical anti-inflammatory drug activity on experimentally induced nickel contact dermatitis: comparison between visual scoring, colorimetry, laser Doppler velocimetry and transepidermal water loss. Skin Pharmacol 3:248–255PubMedGoogle Scholar
  50. Queille-Roussel C, Graeber M, Thurston M, Lachapelle JM, Decroix J, de Cuyper C, Ortonne JP (2000) SDZ ASM 981 is the first non-steroid that suppresses established nickel contact dermatitis elicited by allergen challenge. Contact Dermatitis 42:349–350PubMedCrossRefGoogle Scholar
  51. Rantuccio F, Sinisi D, Scardigno A, Conte A (1978) Histologic aspects of patch test reactions in allergic contact dermatitis. Contact Dermatitis 4:338–342PubMedCrossRefGoogle Scholar
  52. Rullan PP, Barr RJ, Cole GW (1984) Cyclosporine and murine allergic contact dermatitis. Arch Dermatol 120:1179–1183PubMedCrossRefGoogle Scholar
  53. Schnopp C, Remling R, Mohrenschlager M, Weigl L, Ring J, Abeck D (2002) Topical tacrolimus (FK506) and mometasone furoate in treatment of dyshidrotic palmar eczema: A randomized, observer-blinded trial. J Amer Acad Derm 46:73–77CrossRefGoogle Scholar
  54. Schottelius AJ, Giesen C, Asadullah K, Fierro IM, Colgan SP, Bauman J, Guilford W, Perez HD, Parkinson JF (2002) An aspirin-triggered lipoxin A4 stable analog displays a unique topical anti-inflammatory profile. J Immunol 169:7063–7070PubMedGoogle Scholar
  55. Schwarz A, Grabbe S, Riemann H, Aragane Y, Simon M, Manon S, Andrade S, Luger TA, Zlotnik A, Schwarz T (1994) In vivo effects of interleukin-10 on contact hypersensitivity and delayed-type hypersensitivity reactions. J Invest Dermatol 103:211–216PubMedCrossRefGoogle Scholar
  56. Shimada Y, Hasegawa M, Kaburagi Y, Hamaguchi Y, Komura K, Saito E, Takehara K, Steeber DA, Tedder TF, Sato S (2003) L-Selectin or ICAM-1 deficiency reduces an immediate-type hypersensitivity response by preventing mast cell recruitment in repeated elicitation of contact hypersensitivity. J Immunol 170:4325–4334PubMedGoogle Scholar
  57. Sobel RA, Hanzakos JL, Blanchette BW, Williams AM, Dellapelle P, Colvin RB (1987) Anti-T cell monoclonal antibodies in vivo. I. Inhibition of delayed hypersensitivity but not cutaneous basophil hypersensitivity reactions. J Immunol 138:2500–2506PubMedGoogle Scholar
  58. Tani M, Murata Y, Harada S, Takashima T, Horikawa T (1989) Increased contact hypersensitivity response in mice by topical application of 1 alpha,25-dihydroxyvitamin D3 to elicitation site. Arch Dermatol Res 281:355–361PubMedCrossRefGoogle Scholar
  59. Tarayre JP, Barbara M, Aliaga M, Tisne-Versailles J (1990) Comparative actions of immunosuppressants, glucocorticoids and non-steroidal anti-inflammatory drugs on various models of delayed hypersensitivity and on a non-immune inflammation in mice. Arzneimittelforschung 40:1125–1131PubMedGoogle Scholar
  60. Traidl C, Sebastiani S, Albanesi C, Merk HF, Puddu P, Girolomoni G, Cavani A (2000) Disparate cytotoxic activity of nickel-specific CD8+ and CD4+ T cell subsets against keratinocytes. J Immunol 165:3058–3064PubMedGoogle Scholar
  61. Trautmann A, Akdis M, Brocker E-B, Blaser K, Akdis CA (2001) New insights into the role of T cells in atopic dermatitis and allergic contact dermatitis. Trends in Immunology 22:530–532PubMedCrossRefGoogle Scholar
  62. Ulrich P, Grenet O, Bluemel J, Vohr HW, Wiemann C, Grundler O, Suter W (2001) Cytokine expression profiles during murine contact allergy: T helper 2 cytokines are expressed irrespective of the type of contact allergen. Arch Toxicol 75:470–479PubMedCrossRefGoogle Scholar
  63. Vana G, Meingassner JG (2000) Morphologic and immunohistochemical features of experimentally induced allergic contact dermatitis in Gottingen minipigs. Vet Pathol 37:565–580PubMedCrossRefGoogle Scholar
  64. Verma KK, Manchanda Y, Pasricha JS (2000) Azathioprine as a cortico-steroid sparing agent for the treatment of dermatitis caused by the weed Parthenium. Acta Derm Venereol 80:31–32PubMedCrossRefGoogle Scholar
  65. Wang B, Feliciani C, Freed I, Cai Q, Sauder DN (2001) Insights into molecular mechanisms of contact hypersensitivity gained from gene knockout studies. J Leukoc Biol 70:185–191PubMedGoogle Scholar
  66. Webb EF, Tzimas MN, Newsholme SJ, Griswold DE (1998) Intralesional cytokines in chronic oxazolone-induced contact sensitivity suggest roles for tumor necrosis factor-α and interleukin-4. J Invest Dermatol 111(1): 86–92PubMedCrossRefGoogle Scholar
  67. Wendt H, Mugglestone CJ, Wiseman RA (1978) A study of the comparative efficacy of diflucortolone valerate 0.3% ointment and clobetasol propionate 0.05% ointment. Br J Dermatol 99:411–416PubMedCrossRefGoogle Scholar
  68. Williams I, Ort R, Kupper T (1994) Keratinocyte expression of B7-1 in transgenic mice amplifies the primary immune response to cutaneous antigens. PNAS 91:12780–12784PubMedCrossRefGoogle Scholar
  69. Xia Y-P, Li B, Hylton D, Detmar M, Yancopoulos GD, Rudge JS (2003) Transgenic delivery of VEGF to the mouse skin leads to an inflammatory condition resembling human psoriasis. Blood: 2002-2012-3793Google Scholar
  70. Xu H, Heeger PS, Fairchild RL (1997) Distinct roles for B7-1 and B7-2 determinants during priming of effector CD8+ Tcl and regulatory CD4+ Th2 cells for contact hypersensitivity. J Immunol 159(9):4217–4226PubMedGoogle Scholar
  71. Yang X, Corvalan J, Wang P, Roy C, Davis C (1999) Fully human anti-interleukin-8 monoclonal antibodies: potential therapeutics for the treatment of inflammatory disease states. J Leukoc Biol 66:401–410PubMedGoogle Scholar
  72. Yawalkar S, Wiesenberg-Boettcher I, Gibson JR, Siskin SB, Pignat W (1991) Dermatopharmacologic investigations of halobetasol propionate in comparison with clobetasol 17-propionate. J Am Acad Dermatol 1991 Dec;25(6 Pt2):1137–1114PubMedCrossRefGoogle Scholar
  73. Zaumseil RP, Kecskes A, Tauber U, Topert M (1992) Methylprednisolone aceponate — a new therapeutic for eczema: A pharmacological overview. J Dermatol Treat 3:3–7CrossRefGoogle Scholar
  74. Zugel U, Steinmeyer A, Giesen C, Asadullah K (2002) A novel immunosuppressive lalpha,25-dihydroxyvitamin D3 analog with reduced hypercalcemic activity. J Invest Dermatol 119:1434–1442PubMedCrossRefGoogle Scholar
  75. Zweiman B, Moskovitz AR, von Allmen C (1998) Comparison of inflammatory events during developing immunoglobulin E-mediated late-phase reactions and delayed-hypersensitivity reactions. Clin Diagn Lab Immunol 5:574–577PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • T. M. Zollner
    • 1
  • F. H. Igney
    • 1
  • K. Asadullah
    • 1
  1. 1.Corporate Research Business Area DermatologySchering AGBerlinGermany

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