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Mechanisms of Irritant Contact Dermatitis

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Contact Dermatitis

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  1. Piguet PF, Grau GE, Hauser C, Vassalli P (1991) Tumor necrosis factor is a critical mediator in hapten-induced irritant and contact hypersensitivity reactions. J Exp Med 173:673–679

    Article  PubMed  CAS  Google Scholar 

References

  1. Cua AB, Wilhelm KP, Maibach HI (1990) Frictional properties of human skin: Relation to age, sex and anatomical region, stratum corneum hydration and transepidermal water loss. Br J Dermatol 123:473–479

    PubMed  CAS  Google Scholar 

  2. Berardesca E, Maibach HI (1988) Racial differences in sodium lauryl sulphate induced cutaneous irritation: black and white. Contact Dermatitis 18:65–70

    Article  CAS  Google Scholar 

  3. Judge MR, Griffiths HA, Basketter DA, White IR, Rycroft RJ, McFadden JP (1996) Variation in response of human skin to irritant challenge. Contact Dermatitis 34:115–117

    Article  PubMed  CAS  Google Scholar 

  4. Frosch PJ, Kligman AM (1977) A method for appraising the stinging capacity of topically applied substances. J Soc Cosm Chem 28:197–209

    Google Scholar 

  5. Frosch P (1985) Hautirritation und empfindliche haut. Grosse, Berlin

    Google Scholar 

  6. Luger TA, stadler BM, Katz SI, Oppenheim JJ (1981) Epidermal cell (keratinocyte)-derived thymocyte-activating factor (ETAF). J Immunol 127:1493–1498

    CAS  Google Scholar 

  7. Sauder DN, Carter CS, Katz SI, Oppenheim JJ (1982) Epidermal cell production of thymocyte activating factor (ETAF). J Invest Dermatol 79:34–39

    Article  PubMed  CAS  Google Scholar 

  8. Lampert IA (1984) Expression of HLA-DR (ia like) antigen on epidermal keratinocytes in human dermatoses. Clin Exp Immunol 57:93–100

    PubMed  CAS  Google Scholar 

  9. Volc-Platzer B, Steiner A, Radaszkiewicz T, Wolff K (1988) Recombinant gamma interferon and in vivo induction of HLA-DR antigens. Br J Dermatol 119:155–160

    PubMed  CAS  Google Scholar 

  10. Dustin ML, Singer KH, Tuck DT, Springer TA (1988) Adhesion of T lymphoblasts to epidermal keratinocytes is regulated by interferon gamma and is mediated by intercellular adhesion molecule 1 (ICAM-1). J Exp Med 167:1323–1340

    Article  PubMed  CAS  Google Scholar 

  11. Norris P, Poston RN, Thomas DS, Thornhill M, Hawk J, Haskard DO (1991) The expression of endothelial leukocyte adhesion molecule-1 (ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in experimental cutaneous inflammation: a comparison of ultraviolet B erythema and delayed hypersensitivity. J Invest Dermatol 96:763–770

    Article  PubMed  CAS  Google Scholar 

  12. Haraldsen G, Kvale D, Lien B, Farstad IN, Brandtzaeg P (1996) Cytokine-regulated expression of E-selektin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in human microvascular endothelial cells. J Immunol 156:2558–2565

    PubMed  CAS  Google Scholar 

  13. Langerhans P (1868) Über die Nerven der menschlichen Haut. Virchows Arch (Pathol Anat) 44:325–337

    Article  Google Scholar 

  14. Lore K, Sonerborg A, Spetz AL, Andersson U, Andersson J (1998) Erratum to “Immunocytochemical detection of cytokines and chemokines in Langerhans cells and in vitro derived dendritic cells”. J Immunol Methods 218:173–187

    Article  PubMed  CAS  Google Scholar 

  15. Meunier L, Bata-Csorgo Z, Cooper KD (1995) In human dermis, ultraviolet radiation induces expansion of a CD36+ CD11b+ CD1− macrophage subset by infiltration and proliferation; CD1+ Langerhans-like dendritic antigenpresenting cells are concomitantly depleted. J Invest Dermatol 105:782–788

    Article  PubMed  CAS  Google Scholar 

  16. Baadsgaard O, Fox DA, Cooper KD (1988) Human epidermal cells from ultraviolet light-exposed skin preferentially activate autoreactive CD4+2H4+ suppressor-inducer lymphocytes and CD8+ suppressor/cytotoxic lymphocytes. J Immunol 140:1738–1744

    CAS  Google Scholar 

  17. Baadsgaard O, Salvo B, Manni A, Dass B, Fox DA, Cooper KD (1990) In vivo ultraviolet-exposed human epidermal cells activate T suppressor cell pathways that involve CD4+CD45RA+ suppressor-inducer T cells. J Immunol 145:2854–2861

    PubMed  CAS  Google Scholar 

  18. Kang K, Gilliam AC, Chen G, Tootell E, Cooper KD (1998) In human skin, UVB initiates early induction of IL-10 over IL-12 preferentially in the expanding dermal monocytic/macrophagic population. J Invest Dermatol 111:31–38

    Article  PubMed  CAS  Google Scholar 

  19. Lisby S, Baadsgaard O, Cooper KD, Hansen ER, Mehregan D, Thomsen K, Vejlsgaard GL (1990) Phenotype, ultrastructure and function of CD1+DR+ epidermal cells that express CD36 (OKM5) in cutaneous T cell lymphoma. Scand J Immunol 32:111

    PubMed  CAS  Google Scholar 

  20. Baadsgaard O, Lisby S, Avnstorp C, Clemmensen O, Vejlsgaard GL (1990) Antigen-presenting activity of non-Langerhans epidermal cells in contact hypersensitivity reactions. Scand J Immunol 32:217–224

    CAS  Google Scholar 

  21. Hansen ER, Baadsgaard O, Lisby S, Cooper KD, Thomsen K, Vejlsgaard GL (1990) Cutaneous T-cell lymphoma lesional epidermal cells activate autologous CD4+ T lymphocytes: involvement of both CD1+OKM5+ and CD1+OKM5− antigen-presenting cells. J Invest Dermatol 94:485–491

    Article  PubMed  CAS  Google Scholar 

  22. Lisby S, Baadsgaard O, Cooper KD, Vejlsgaard GL (1989) Decreased number and function of antigen-presenting cells in the skin following application of irritant agents: relevance for skin cancer? J Invest Dermatol 92:842–847

    Article  PubMed  CAS  Google Scholar 

  23. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136:2348–2357

    PubMed  CAS  Google Scholar 

  24. Kondo S, Kono T, Sauder DN, McKenzie RC (1993) IL-8 gene expression and production in human keratinocytes and their modulation by UVB. J Invest Dermatol 101:690–694

    Article  PubMed  CAS  Google Scholar 

  25. Pitzalis C, Cauli A, Pipitone N, Smith C, Barker J, Marchesoni A, Yanni G, Panayi GS (1996) Cutaneous lymphocyte antigen-positive T lymphocytes preferentially migrate to the skin but not to the joint in psoriatic arthritis. Arthritis Rheum 39:137–145

    PubMed  CAS  Google Scholar 

  26. Santamaria LF, Perez Soler MT, Hauser C, Blaser K (1995) Allergen specificity and endothelial transmigration of T cells in allergic contact dermatitis and atopic dermatitis are associated with the cutaneous lymphocyte antigen. Int Arch Allergy Immunol 107:359–362

    Article  PubMed  CAS  Google Scholar 

  27. Santamaria Babi LF, Picker LJ, Perez Soler MT, Drzimalla K, Flohr P, Blaser K, Hauser C (1995) Circulating allergenreactive T cells from patients with atopic dermatitis and allergic contact dermatitis express the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen. J Exp Med 181:1935–1940

    Article  Google Scholar 

  28. Brasch J, Burgard J, Sterry W (1992) Common pathogenetic pathways in allergic and irritant contact dermatitis. J Invest Dermatol 98:166–170

    Article  PubMed  CAS  Google Scholar 

  29. Scheynius A, Fischer T, Forsum U, Klareskog L (1984) Phenotypic characterization in situ of inflammatory cells in allergic and irritant contact dermatitis in man. Clin Exp Immunol 55:81–90

    PubMed  CAS  Google Scholar 

  30. Lavrijsen APM (1997) Stratum corneum barrier in healthy and diseased skin. PhD Thesis, Leiden University, pp 26–38

    Google Scholar 

  31. Agner T, Serup J (1993) Time course of occlusive effects on skin evaluated by measurement of transepidermal water loss (TEWL). Including patch tests with sodium lauryl sulphate and water. Contact Dermatitis 28:6–9

    Article  PubMed  CAS  Google Scholar 

  32. De Fine Olivarius F, Agner T, Menné T (1993) Skin barrier function and dermal inflammation. An experimental study of transepidermal water loss after dermal tuberculin injection compared with SLS patch testing. Br J Dermatol 129:554–557

    Google Scholar 

  33. Lee JY, Effendy I, Maibach HI (1997) Acute irritant contact dermatitis: recovery time in man. Contact Dermatitis 36:285–290

    Article  CAS  Google Scholar 

  34. Wilhelm KP, Cua AB, Wolf HH, Maibach HI (1993) Surfactant-induced stratum corneum hydration in vivo: prediction of the irritant potential of anionic surfactants. J Invest Dermatol 101:310–315

    Article  PubMed  CAS  Google Scholar 

  35. Fartasch M, Schnetz E, Diepgen TL (1998) Characterization of detergent-induced barrier alterations — effect of barrier cream on irritation. J Invest Dermatol 3:121–127

    CAS  Google Scholar 

  36. Fischer LB, Maibach HI (1975) Effect of some irritants on human epidermal mitosis. Contact Dermatitis 1:273–276

    Article  Google Scholar 

  37. Wood LC, Jackson SM, Elias PM, Grunfeld C, Feingold KR (1992) Cutaneous barrier perturbation stimulates cytokine production in the epidermis of mice. J Clin Invest 90:482–487

    Article  PubMed  CAS  Google Scholar 

  38. Willis CM, Stephens CJM, Wilkinson JD (1989) Epidermal damage induced by irritants in man: a light and electron microscopic study. J Invest Dermatol 93:695–699

    Article  PubMed  CAS  Google Scholar 

  39. Willis CM, Young E, Brandon DR, Wilkinson JD (1986) Immunopathological and ultrastructural findings in human allergic and irritant contact dermatitis. Br J Dermatol 115:305–316

    PubMed  CAS  Google Scholar 

  40. Avnstorp C, Ralfkiaer E, Jørgensen J, Wantzin GL (1987) Sequential immunophenotypic study of lymphoid infiltrate in allergic and irritant reactions. Contact Dermatitis 16:239–245

    Article  PubMed  CAS  Google Scholar 

  41. Hoefakker S, Caubo M, van’t Erve EH, Roggeveen MJ, Boersma WJ, van Joost T, Notten WR, Claassen E (1995) In vivo cytokine profiles in allergic and irritant contact dermatitis. Contact Dermatitis 33:258–266

    Article  PubMed  CAS  Google Scholar 

  42. Jung K, Linse F, Pals ST, Heller R, Moths C, Neumann C (1997) Adhesion molecules in atopic dermatitis: patch tests elicited by house dust mite. Contact Dermatitis 37:163–172

    Article  PubMed  CAS  Google Scholar 

  43. De Vries IJ, Langeveld-Wildschut EG, van Reijsen FC, Bihari IC, bruijnzeel-Koomen CA, Thepen T (1997) Nonspecific T-cell homing during inflammation in topic dermatitis: expression of cutaneous lymphocyte-associated antigen and integrin alphaE beta7 on skin-infiltrating T cells. J Allergy Clin Immunol 100:694–701

    Article  PubMed  Google Scholar 

  44. Santamaria Babi LF, Moser R, Perez Soler MT, Picker LJ, Blaser K, Haser C (1995) Migration of skin-homing T cells across cytokine-activated human endothelial cell layers involves interaction of the cutaneous lymphocyte-associated antigen (CLA), the very late antigen-4 (VLA-4), and the lymphocyte function-associated antigen-1 (LFA-1). J Immunol 154:1543–1550

    Google Scholar 

  45. Van de Sandt JJ, Bos TA, Rutten AA (1995) Epidermal cell proliferation and terminal differentiation in skin organ culture after topical exposure to sodium dodecyl sulphate. In Vitro Cell Dev Biol Anim 31:761–766

    Google Scholar 

  46. Gawkrodger DJ, Carr MM, McVittie E, Guy K, Hunter JA (1987) Keratinocyte expression of MHC class II antigens in allergic sensitization and challenge reactions and in irritant contact dermatitis. J Invest Dermatol 88:11–16

    Article  PubMed  CAS  Google Scholar 

  47. Gatto H, Viac J, Charveron M, Schmitt D (1992) Study of immune-associated antigens (IL-1 and ICAM-1) in normal human keratinocytes treated with sodium lauryl sulphate. Arch Dermatol Res 284:186–188

    Article  PubMed  CAS  Google Scholar 

  48. Henseleit U, Steinbrink K, Goebeler M, Roth J, Vestweber D, Sorg C, Sunderkotter C (1996) E-selectin expression in experimental models of inflammation in mice. J Pathol 180:317–325

    Article  PubMed  CAS  Google Scholar 

  49. Mikulowska A, Falck B (1994) Distributional changes of Langerhans cells in human skin during irritant contact dermatitis. Arch Dermatol Res 286:429–433

    Article  PubMed  CAS  Google Scholar 

  50. Ranki A, Kanerva L, Forstrom L, Konttinen Y, Mustakallio KK (1983) T and B lymphocytes, macrophages and Langerhans’ cells during the course of contact allergic and irritant skin reactions in man. Acta Derm Venerol 63:376–383

    PubMed  CAS  Google Scholar 

  51. Marks JG Jr, Zaino RJ, Bressler MF, Williams JV (1987) Changes in lymphocyte and Langerhans cell populations in allergic and irritant contact dermatitis. Int J Dermatol 26:354–357

    PubMed  Google Scholar 

  52. Brand CU, Hunziker T, Braathen LR (1992) Studies on human skin lymph containing Langerhans cells from sodium lauryl sulphate contact dermatitis. J Invest Dermatol 99:109S–110S

    Article  PubMed  CAS  Google Scholar 

  53. Brand CU, Hunziker T, Limat A, Braathen LR (1993) Large increase of Langerhans cells in human skin lymph derived from irritant contact dermatitis. Br J Dermatol 128:184–188

    PubMed  CAS  Google Scholar 

  54. Forsey RJ, Shahidullah H, Sands C, McVittie E, Aldridge RD, Hunter JA, Howie SE (1998) Epidermal Langerhans cell apoptosis is induced in vivo by nonanoic acid but not by sodium lauryl sulphate. Br J Dermatol 139:453–461

    Article  PubMed  CAS  Google Scholar 

  55. Haas J, Lipkow T, Mohamadzadeh M, Kolde G, Knop J (1992) Induction of inflammatory cytokines in murine keratinocytes upon in vivo stimulation with contact sensitizers and tolerizing analogues. Exp Dermatol 1:76–83

    Article  PubMed  CAS  Google Scholar 

  56. Kondo S, Pastore S, Shivji GM, McKenzie RC, Sauder DN (1994) Characterization of epidermal cytokine profiles in sensitization and elicitation phases of allergic contact dermatitis as well as irritant contact dermatitis in mouse skin. Lymphokine Cytokine Res 13:367–375

    PubMed  CAS  Google Scholar 

  57. Hunziker T, Brand CU, Kapp A, Waelti ER, Braathen LR (1992) Increased levels of inflammatory cytokines in human skin lymph derived from sodium lauryl sulphate-induced contact dermatitis. Br J Dermatol 127:254–257

    PubMed  CAS  Google Scholar 

  58. Holliday MR, Corsini E, Smith S, Basketter DA, Dearman RJ, Kimber I (1997) Differential induction of cutaneous TNF-α and IL-6 by topically applied chemicals. Am J Contact Dermatitis 8:158–164

    Article  PubMed  CAS  Google Scholar 

  59. Mohamadzadeh M, Muller M, Hultsch T, Enk A, Saloga J, Knop J (1994) Enhanced expression of IL-8 i normal human keratinocytes and human keratinocyte cell line HaCaT in vitro after stimulation with contact sensitizers, tolerogens and irritants. Exp Dermatol 3:298–303

    Article  PubMed  CAS  Google Scholar 

  60. Enk AH, Katz SI (1992) Early molecular events in the induction phase of contact sensitivity. Proc Natl Acad Sci USA 89:1398–1402

    Article  PubMed  CAS  Google Scholar 

  61. Piguet PF, Grau GE, Hauser C, Vassalli P (1991) Tumor necrosis factor is a critical mediator in hapten-induced irritant and contact hypersensitivity reactions. J Exp Med 173:673–679

    Article  PubMed  CAS  Google Scholar 

  62. Lisby S, Muller KM, Jongeneel CV, Saurat JH, Hauser C (1995) Nickel and skin irritants up-regulate tumor necrosis factor-alpha mRNA in keratinocytes by different but potentially synergistic mechanisms. Int Immunol 7:343–352

    PubMed  CAS  Google Scholar 

  63. Grängsjö A, Leijon-Kuligowski A, Torma H, Roomans GM, Lindberg M (1996) Different pathways in irritant contact eczema? Early differences in the epidermal element content and expression of cytokines after application of 2 different irritants. Contact Dermatitis 35:355–360

    Article  PubMed  Google Scholar 

  64. Wilmer JL, Burleson FG, Kayama F, Kanno J, Luster MI (1994) Cytokine induction in human epidermal keratinocytes exposed to contact irritants and its relation to chemical-induced inflammation in mouse skin. J Invest Dermatol 102:915–922

    Article  PubMed  CAS  Google Scholar 

  65. Zepter K, Haffner A, Soohoo LF, de Luca D, Tang HP, Fisher P, Chavinson J, Elmets CA (1997) Induction of biologically active IL-1 beta-converting enzyme and mature IL-1 beta in human keratinocytes by inflammatory and immunogic stimuli. J Immunol 159:6203–6208

    PubMed  CAS  Google Scholar 

  66. Luger T (1991) The epidermis as a source of immunomodulating cytokines. Period Biol 93:97–104

    CAS  Google Scholar 

  67. Lee SV, Morhenn VB, Ilnicka M, Eugui EM, Allison AC (1991) Autocrine stimulation of interleukin-1 alpha and transforming growth factor alpha production in human keratinocytes and its antagonism by glucocorticoids. J Invest Dermatol 97:106–110

    Article  PubMed  CAS  Google Scholar 

  68. McKenzie RC, Sauder DN (1990) The role of keratinocyte cytokines in inflammation and immunity. J Invest Dermatol 95:105S–107S

    Article  PubMed  CAS  Google Scholar 

  69. Gearing AJH, Beckett P, Christodoulou M, Churchill M, Clements J, Davidson AH, Drummond AH, Galloway WA, Gilbert R, Gordon JL (1994) Processing of tumour necrosis factor-alpha precursor by metalloproteinases. Nature 370:555–557

    Article  PubMed  CAS  Google Scholar 

  70. Trefzer U, Brockhaus M, Loetscher H, Parlow F, Kapp A, Schopf E, Krutmann J (1991) 55-kD tumor necrosis factor receptor is expressed by human keratinocytes and plays a pivotal role in regulation of human keratinocyte ICAM-1 expression. J Invest Dermatol 97:911–916

    Article  PubMed  CAS  Google Scholar 

  71. Groves RW, Allen MH, Ross EL, Barker JN, MacDonald DM (1995) Tumour necrosis factaor alpha is pro-inflammatory in normal human skin and modulates cutaneous adhesion molecule expression. Br J Dermatol 132:345–352

    PubMed  CAS  Google Scholar 

  72. Detmar M, Orfanos CE (1990) Tumor necrosis factor-alpha inhibits cell proliferation and induces class II antigens and cell adhesion molecules in cultured normal human keratinocytes in vitro. Arch Dermatol Res 282:238–245

    Article  PubMed  CAS  Google Scholar 

  73. Yamazaki S, Yokozeki H, Satoh T, Katayama I, Nishioka K (1998) TNF-alpha, RANTES, and MCP-1 are major chemoattractants of murine Langerhans cells to the regional lymph nodes. Exp Dermatol 7:35–41

    PubMed  CAS  Google Scholar 

  74. Wang B, Kondo S, Shivji GM, Fujisawa H, Mak TW, Sauder DN (1996) Tumour necrosis factor receptor II (p75) signaling is required for the migration of Langerhans’ cells. Immunology 88:284–288

    PubMed  CAS  Google Scholar 

  75. Corsini E, Terzoli A, Bruccoleri A, Marinovich M, Galli CL (1997) Induction of necrosis factor-α in vivo by a skin irritant. Tributyltin, through activation of transcription factors: its pharmacological modulation by anti-inflammatory drugs. J Invest Dermatol 108:892–896

    Article  PubMed  CAS  Google Scholar 

  76. Zuckerman SH, Evans GF, Guthrie L (1991) Transcriptional and post-transcriptional mechanisms involved in the differential expression of LPS-induced IL-1 and TNF mRNA. Immunology 73:460–465

    PubMed  CAS  Google Scholar 

  77. Kamado K, Sato K (1994) Regulation of IL-1a expression in human karatinocytes. Lymphokine Cytokine Res 13:29–35

    Google Scholar 

  78. Warner SJC, Auger KR, Libby P (1987) Interleukin-1 induces interleukin-1. J Immunol 139:1911–1917

    PubMed  CAS  Google Scholar 

  79. Lisby S, Hauser C (2002) Transcriptional regulation of tumor necrosis factor-α in keratinocytes mediated by interleukin-1Gb and tumor necrosis factor-α. Exp Dermatol 11:592–598

    Article  PubMed  CAS  Google Scholar 

  80. Zachariae CO, Jinquan T, Nielsen V, Kaltoft K, Thestrup-Pedersen K (1992) Phenotypic determination of T-lymphocytes responding to chemotactic stimulation from fMLP, IL-8, human IL-10, and epidermal lymphocyte chemotactic factor. Arch Dermatol Res 284:333–338

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Genmab A/S, Toldbodgade 55B, 1253, Copenhagen K, Denmark

    Steen Lisby

  2. Genmab A/S, Copenhagen, Denmark

    Ole Baadsgaard

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  1. Steen Lisby
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  2. Ole Baadsgaard
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Editors and Affiliations

  1. Klinikum Dortmund gGmbH, Hautklinik Lehrstuhl Dermatologie der Universität Witten/Herdecke, Beurhausstr. 40, 44137, Dortmund, Germany

    Peter J. Frosch (Professor) (Professor)

  2. Dermatologisk afdeling K, Amtssygehuset Gentofte, 2900, Hellerup, Denmark

    Torkil Menné (Professor Dr.) (Professor Dr.)

  3. Laboratoire de Dermato-Chimie Clinique Dermatologique, CHU, 67091, Strasbourg Cedex, France

    Jean-Pierre Lepoittevin (Professor) (Professor)

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Lisby, S., Baadsgaard, O. (2006). Mechanisms of Irritant Contact Dermatitis. In: Frosch, P.J., Menné, T., Lepoittevin, JP. (eds) Contact Dermatitis. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-31301-X_4

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  • DOI: https://doi.org/10.1007/3-540-31301-X_4

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