Mechanisms of drug-induced delayed-type hypersensitivity reactions in the skin

AAPS Journal

Volumn 7, Issue 4, 2005, Pages

  Roychowdhury, Sanjoy ^a   Svensson, Craig K ^a  

^a UNIVERSITY OF IOWA   (United States)

Author keywords

Cutaneous drug reactions; Cytokines; Delayed type hypersensitivity; Dendritic cells; Keratinocytes; T cells

Indexed keywords

ABACAVIR; ANALGESIC AGENT; ANESTHETIC AGENT; ANTICONVULSIVE AGENT; ANTIINFECTIVE AGENT; CARBAMAZEPINE; CARDIOVASCULAR AGENT; CD4 ANTIGEN; CD8 ANTIGEN; CLOZAPINE; CYTOKINE; DAPSONE; DICLOFENAC; ESTROGEN; HAPTEN; HYDRALAZINE; IMMUNOGLOBULIN; LIDOCAINE; NEUROLEPTIC AGENT; NITRIC OXIDE; NONSTEROID ANTIINFLAMMATORY AGENT; PARACETAMOL; PENICILLIN G; PROCAINAMIDE; REACTIVE OXYGEN METABOLITE; STEROID; SULFAMETHOXAZOLE; SULFONAMIDE; UNINDEXED DRUG; XENOBIOTIC AGENT; DRUG;

ANGIONEUROTIC EDEMA; ANTIGEN PRESENTATION; CONTACT DERMATITIS; DELAYED HYPERSENSITIVITY; DENDRITIC CELL; DRUG ERUPTION; DRUG FATALITY; DRUG HYPERSENSITIVITY; DRUG INDUCED DISEASE; DRUG MECHANISM; ECZEMA; ERYTHEMA MULTIFORME; FEVER; HUMAN; IMMUNE RESPONSE; KERATINOCYTE; MEDIATOR RELEASE; NONHUMAN; RASH; REVIEW; SKIN DEFECT; SKIN INFLAMMATION; STEVENS JOHNSON SYNDROME; T LYMPHOCYTE; CHEMICALLY INDUCED DISORDER; IMMUNOLOGY; METABOLISM; SKIN; SKIN DISEASE;

DRUG HYPERSENSITIVITY; HUMANS; HYPERSENSITIVITY, DELAYED; PHARMACEUTICAL PREPARATIONS; SKIN; SKIN DISEASES;

EID: 33747103575     PISSN: 15221059     EISSN: 15221059     Source Type: Journal    
DOI: 10.1208/aapsj070480     Document Type: Review

References (170)

1. Pirmohamed M, Breckenridge A, Kitteringham N, et al. Adverse drug reactions. BMJ. 1998;316:1295-1298.
2. Vervloet D, Durham S. Adverse reactions to drugs. BMJ. 1998;316:11511-1514.
3. Naisbitt DJ. Drug hypersensitivity reactions in skin: understanding mechanisms and the development of diagnostic and predictive tests. Toxicology. 2004; 194:179-196.
4. Svensson CK, Cowen EW, Gaspari AA Cutaneous drug reactions. Pharmacol Rev. 2001;53:357-379.
5. Romano A, Torres MJ,, Quaratino D, et al. Diagnostic evaluation or delayed hypersensitivity to systematically administered drugs. Allergy. 1999;54:23-27.
6. Saint-Mezard P, Rosieres A, Krasteva M, et al. Allergic contact dermatitis, Eur J DermatoL 2004:14:284-295.
7. Sertoli A, Francalanci S, Acciai MC, et al. Epidemiological survey of contact dermatitis in Italy (1984-1993) by GIRDCA (Gruppo Italiano Ricerca Dermatiti da Contatto e Ambientali). Am J Contact Dermat. 1999;10:18-30.
8. Matulich J, Sullivan J. A temporary henna tattoo causing hair and clothing dye allergy. Contact Dermatitis. 2005;53:33-36.
9. Militello G, James W. Lyral: a fragrance allergen. Dermatitis. 2005;16.41-44.
10. Bonamonte D, Foti C, Antelmi AR, et al. Nickel contact allergy and menstrual cycle. Contact Dermatitis. 2005;52:309-313.
11. Li LY, Jr, Cruz PD, Jr. Allergic contact dermatitis: pathophysiology applied to future therapy. Dermatol Ther. 2004;17:219-223.
12. Jensen C, Lisby S, Larsen J, et al. Characterization of lymphocyte subpopulations and cytokine profiles in peripheral blood of nickel-sensitive individuals with systemic contact dermatitis after oral nickel exposure. Contact Dermatitis. 2004;50:31-38.
13. Naldi L, Conforti A, Venegoni M, et al. Cutaneous reactions to drugs: an analysis of spontaneous reports in 4 Italian regions. Br J Clin Pharmacol. 1999;48:839-846.
14. Shepherd GM. Hypersensitivity reactions to drugs: evaluation and management. Mt Sinai J Med. 2003;70:113-125.
15. Knowles SR, Shapiro LE, Shear NH. Anticonvulsant hypersensitivity syndrome: incidence, prevention, and management. Drug Saf. 1999;21:489-501.
16. Aronson JK, Ferner RE. Joining the DoTS: new approach to classifying adverse drug reactions. BMJ. 2003;327:1222-1225.
17. Edwards IR, Aronson JK. Adverse drug reaction: definitions, diagnosis, and management. Lancet. 2000;356:1255-1259.
18. Hari Y, Frutig-Schnyder K, Hurni M, et al, T cell involvement in cutaneous drug eruptions, Clin Exp Allergy. 2001;31-1398-1408.
19. Herti M, Merk HF. Lymphocyte activation in cutaneous drug reactions. J Invest Dermatol. 1995;105:95S-98S.
20. Pichler WJ, Schnyder B, Zanni MP, et al. Role of T cells in drug allergies. Allergy. 1998;53.225-232.
21. Bessmertny O, Hatton R, Gonzalez-Peralta R. Antiepileptic hypersensitivity syndrome in children. Ann Pharmacother. 2001;35:533-538,
22. Yawalkar N. Drug-induced exanthems. Toxicology. 2005;209:131-134.
23. Merk HF. Diagnosis of drug hypersensitivity: lymphocyte transformation test and cytokines. Toxicology. 2005;209:217-220.
24. Britschgi M, Steiner UC, Schmid S, et al. T-cell involvement in drug-induced acute generalized exanthematous pustulosis. J Clin Invest. 2001;107:1433-1441.
25. Miyauchi H, Hosokawa H, Akaeda T, et al. T-cell subsets in drug-induced toxic epidermal necrolysis: possible pathogenic mechanism induced by CD8-positive T cells. Arch Dermatol. 1991;127:851-855.
26. Pichler WJ, T cells in drug allergy. Curr Allergy Asthma Rep. 2002;2:9-15.
27. Kaplan MH, Hall WW, Susin M, et al. Syndrome of severe skin disease, eosinophilia, and dermatopathic lymphadenopathy in patients with HTLV-II complicating human immunodeficiency virus infection. Am J Med. 1991;91:300-309.
28. Mauri-Hellweg D, Beftens F, Mauri D, et al. Activation of drug-specific CD4+ and CD8+ T cells in individuals allergic to sulfonamides, phenytoin, and carbarnazepine. J Immunol. 1995;155:462-472.
29. Schnyder B, Burkhart C, Schnyder-Frutig K, et al, Recognition of sulfamethoxazole and its reactive metabolites by drug-specific CD4+ T cells from allergic individuals. J Immunol, 2000;164:6647-6654.
30. Zanni IVIP, von Greyerz S, Schnyder B, et al. HLA-restricted, processing- and metabolism-independent pathway of drug recognition by human alpha beta T lymphocytes. J Clin Invest 1998;102:1591-1598.
31. Naisbitt DJ, Farrell J, Wong G, et al. Characterization of drug-specific T cells in lamotrigine hypersensitivity. J Allergy Clin Immunol. 2003;111:1393-1403.
32. Nassif A, Bensussan A, Bournsell L, et al. Toxic epidermal necrolysis: effector cells are drug-specific cytotoxic T cells. J Allergy Clin Immunol. 2004;114:1209-1215.
33. Nassif A, Bensussan A, Dorothee G, et al. Drug specific cytotoxic T cells in the skin lesions of a patient with toxic epidermal necrolysis. J Invest Dermatol. 2002;118:728-733.
34. Schnyder B, Frutig K, Mauri-Hellweg D, et al. T-cell-mediated cytotoxicity against keratinocytes in sulfamethoxazol-induced skin reaction. Clin Exp Allergy. 1998;28:1412-1417.
35. Kimbe I, Basketter DA, Gerberick GF, et al. Allergic contact dermatitis. Int Immunopharmacol. 2002;2:201-211.
36. De Smedt AC, Van Den Heuvel RL, Van Tendeloo VF, et al. Capacity of CD34+ progenitor-derived dendritic cells to distinguish between sensitizers and irritants. Toxicol Lett. 2005; 156:377-389.
37. Pichler WJ, Tilch J. The lymphocyte transformation test in the diagnosis of drug hypersensitivity. Allergy. 2004;59:809-820.
38. Romani N, Holzmann S, Tripp CH, et al. Langerhans cells - dendritic cells of the epidermis. APMIS. 2003;111:725-740.
39. Banerjee, G, Damodaran A, Devi N, et al. Role of keratinocytes in antigen presentation and polarization of human T lymphocytes. Scand J Immunol. 2004;59:385-394.
40. Park BK, Kitteringham NR, Powell H, et al. Advances in molecular toxicology: towards understanding idiosyncratic drug toxicity. Toxicology. 2000;153:39-60.
41. Ju C, Uetrecht JP. Detection of 2-hydroxyiminostilbene in the urine of patients taking carbamazepine and its oxidation to a reactive iminoquinone intermediate. J Pharmacol Exp Ther. 1999;288:51-56.
42. Madden S, Maggs JL, Park BK, Bioactivation of carbamazepine in the rat in vivo: evidence for the formation of reactive arene oxide(s). Drug Metab Dispos. 1996;24:469-479.
43. Cribb AF, Miller M, Tesoro A, et al. Peroxidase-dependent oxidation of sulfonamides by monogytes and neutrophils from humans and dogs. Mol Pharmaco/. 1990;38:744-751
44. Cribb AE, Spielberg SP, Griff in GP. N4-hydroxylation of sulfamethoxazole by cytochrome P450 of the cytochrome P4502C subfamily and reduction of sulfamethoxazole hydroxylarnine in human and rat hepatic microsomes. Drug Metab Dispos. 1995;23:406-414.
45. Uetrecht JP, Shear NH, Zahid N. N-chlorination of sulfamethoxazole and dapsone by the myeloperoxidase system. Drug Metab Dispos. 1993;21:830-834.
46. Winter HR, Wang Y, Unadkat JD. CYIP2C8/9 mediate dapsone N-hydroxylation at clinical concentrations of dapsone. Drug Metab Dispos, 2000;28:865-868
47. Mitra AK, Thummel KE, Kalhorn TF, et al. Metabolism of dapsone to its hydroxylamine by CYP2E1 in vitro and in vivo. Clin Pharmacol Ther. 1995;58.556-566.
48. Reilly TP, Lash LH, Doll MA, et al. A role for bioactivation and covalent binding within epidermal keratinocytes in sulfonamide-induced cutaneous drug reactions. J Invest Dermatol. 2000;114:1164-1173.
49. Yan Z, Li J, Huebert N, et al. Detection of a novel reactive metabolite of diclofenac: evidence for CYP2C9-mediated bioactivation via arene oxides. Drug Metab Dispos. 2005;33:706-713.
50. Kumar S, Samuel K, Subramanian R, et al. Extrapolation of diclofenac clearance from in vitro microsomal metabolism data: role of acyl glucuronidation and sequential oxidative metabolism of the acyl glucuronide. J Pharmacol Exp Ther. 2002;303:969-978.
51. Masubuchi Y, Umeda S, Igarashil S, et al. Participation of the CYP2D subfamily in lidocaine 3-hydroxylation and formation of a reactive metabolite covalently bound to liver microsomal protein in rats. Biochem Pharmacol. 1993;46:1867-1869.
52. Walsh JS, Reese MJ, Thurmond LM. The metabolic activation of abacavir by human liver cytosol and expressed human alcohol dehydrogenase isozymes. Chem Biol Interact 2002;142.135-154.
53. Cuttle L, Munns AJ, Hogg NA, et al. Phenytoin metabolism by human cytochrome P450: involvement of P450 3A and 2C forms in secondary metabolism and drug-protein adduct formation Dispos. Drug Metab Dispos. 2000;28:945-950.
54. Uetrecht JP. Reactivity and possible significance of hydroxylamine and nitroso metabolites of procainamide. J Pharmacol Exp Ther. 1985;232:420-425.
55. Swanson HI. Cytochrome P450 expression in human keratinocytes: an aryl hydrocarbon receptor perspective. Chem Biol Interact. 2004; 149:69-79.
56. Janmohamed A, Dolphin CT, Phillips IR, et al. Quantification and cellular localization of expression in human skin of genes encoding flavin-containing monooxygenases and cytochromes P450. Biochem Pharmacol, 2001;62:777-786.
57. Lee JL, Mukhtar H, Bickers DR, et al. Cyclooxygenases in the skin: pharmacological and toxicological implications. Toxicol Appl Pharmacol. 2003;192:294-306.
58. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392:245-252.
59. Randolph GJ. Dendritic cell migration to lymph nodes: cytokines, chemokines, and lipid mediators. Semin Immunol. 2001;13:267-274.
60. Randolph GJ, Angeli V, Swartz MA. Dendritic-cell trafficking to lymph nodes through lymphatic vessels. Nat Rev Immunol. 2005;5:617-628.
61. Kimber I, Cumberbatch M. Dendritic cells and cutaneous immune responses to chemical allergens, Toxicol Appl Pharmacol. 1992;117:137-146.
62. Kimber I, Cumberbatch M, Betts CJ, et al. Dendritic cells and skin sensitization hazard assessment. Toxicol In Vitro. 2004;18:195-202.
63. Shortman K, Liu YJ. Mouse and human dendritic cell subtypes. Nat Rev Immunol. 2002;2:151-161.
64. Becker D, Mohamadzadeh K Reske K, et al. Increased level of intracellular MHC class II molecules in murine Langerhans cells following in vivo and in vitro administration of contact allergens, J Invest Dermatol. 1992;99:545-549.
65. Girolomoni G, Simon JC, Bergstresser PR, et al, Freshly isolated spleen dendritic cells and epidermal Langerhans cells undergo similar phenotypic and functional changes during short-term culture, J Immunol. 1992;145:2820-2826.
66. Neisius U-Brand P, Plochmann S, et al. Detection of increased tyrosine phosphorylation in murine Langerhans cells after stimulation with contact sensitizers. Arch Dermatol Res. 1999;291:22-27.
67. Alba S, Katz SI. Phenotypic and functional characteristics of in vivo-activated langernans cells. J Immunol. 1990;145:2791-2796.
68. Verrier AC, Schmitt D, Staquet MJ. Fragrance and contact allergens in vitro modulate the HLA-DR and Ecadherin expression on human epidermal Langerhans cells. Int Arch Allergy Immunol 1999;120:56-62.
69. Enk AH, Katz SI. Early molecular events in the induction phase of contact sensitivity. Proc Nad Acad Sci USA. 1992;89:1398-1402.
70. Wang B, Feliciani C, Howell BG, et al. Contribution of Langerhans cell-derived IL-18 to contact hypersensitivity. J Immunol. 2002;168:3303-3308.
71. Kessler BM, Glas R, Ploegh HL. MHC class I antigen processing regulated by cytosolic proteolysis-short cuts that alter peptide generation. Mol Immunol. 2002;39:171-179.
72. Cresswell P. Assembly, transport, and function of MHC class II molecules. Annu Rev Immunol. 1994;12:259-293.
73. Cresswell P, Androlewicz MJ, Ortmann B. Assembly and transport of class I MHC-peptide complexes. Ciba Found Symp. 1994;187:150-162.
74. Park BK, Pirmohamed M, Kitteringham NR. Role of drug disposition in drug hypersensitivity: a chemical, molecular, and clinical perspective. Chem Res Toxic& 1998;11:969-988.
75. Herouet C, Cottin M, LeClaire J, et al. Contact sensitizers specifically increase MHC class II expression on murine immature dendritic cells. In Vitr Mol Toxicol. 2000;13:113-123.
76. Cumberbatch M, Dearman RJ, Griffiths CE, et al. Epidermal Langerhans cell migration and sensitization to chemical allergens. APMIS. 2003;111:797-804.
77. Mizuashi M, Ohtani T, Nakagawa S, et al. Redox imbalance induced by contact sensitizers triggers the maturation of dendritic cells. J Invest Dermatol, 2005;124.579-586.
78. Chambers CA, Allison JP. Costimulation in T cell responses. Curr Opin Immunol. 1997,9:396-404.
79. McAdam AJ, Schweitzer AN, Sharpe AH, The role of B7 costimulation in activation and differentiation of CD4+ and CD8+ T cells. Immunol Rev. 1998; 165:231-247.
80. Hochweller K, Anderton SM. Kinetics of costimulatory molecule expression by T cells and dendritic cells during the induction of tolerance versus immunity in vivo. Eur J Immunol. 2005;35:1086-1096.
81. Yokozeki H, Takayama K, Ohki O, et al. Comparative analysis of CD80 and CD86 on human Langerhans calls: expression and function. Arch Dermatol Res. 1998;290:547-552.
82. Wakem P, Jr, Burns RP, Jr, Ramirez F, et al. Allergens and irritants transcriptionally upregulate CD80 gene expression in human keratinocytes. J Invest Dermatol. 2000;114:1085-1092.
83. Fabbri M, Smart C, Pardi R. T lymphocytes. Int J Biochem Cell Biol, 2003;35:1004-1008.
84. Yawalkar N, Hari Y, Frutig K, et al. T cells isolated from positive epicutaneous test reactions to amoxicillin and ceftriaxone are drug specific and cytotoxic. J Invest Dermatol. 2000;115:647-652.
85. Naisbitt DJ, Britschgi M, Wong G, et al. Hypersensitivity reactions to carbamazepine: characterization of the specificity, phenotype, and cytokine profile of drug-specific T cell clones. Mol Pharmacol. 2003;63:732-741
86. Schnyder B, Mauri-Hellweg D, Zanni M, et al. Direct, MHC-dependent presentation of the drug sulfamethoxazole to human alphabeta. T cell clones. J Clin Invest, 1997;100:136-141.
87. Zanni MP. Mauri-Hellweg D, Brander C, et al. Characterization of lidocaine-specific T cells. J Immunol. 1997;158:1139-1148.
88. Zanni MP, von Greyerz S, Hari Y, et al. Recognition of local anesthetics by alphabeta+ T cells. J Invest Dennatol. 1999;112:197-204.
89. Gerber BO, Pichler WJ. Cellular mechanisms of T cell mediated drug hypersensitivity. Curr Opin Immunol. 2004;16:732-737.
90. Gerber BO, Pichler WJ. Noncovaleńt interactions of drugs with immune receptors may mediate drug-induced hypersensitivity reactions. AAPS J. In press.
91. Santamaria Babi LF, Perez Soler MT, Hauser C, et al. Skin-homing T cells in human cutaneous allergic inflammation. Immunol Res. 1995-$14:317-324.
92. Santamaria LF, Perez Soler MT, Hauser C, et al. 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. 1995;107:359-36
93. Pichler WJ, Yawalkar N, Britschgi M, et al. Cellular and molecular pathophysiology of cutaneous drug reactions. Am J Clin Dermatol. 2002;3:229-238.
94. Nickoloff BJ, Turka LA. Immunological functions of nonprofessional antigen-presenting cells: new insights from studies of T-cell interactions with keratinocytes. Immunol Today. 1994;15:464-469
95. Wikner NE, Huff JC, Norris DA, et al. Study of HLA-DR synthesis in cultured human keratinocytes. J Invest Dermatol. 1986;87:559-564.
96. Meunier L, Vian L, Lagoueyte C, et al. Quantification of CD1a, HLA-DR, and HLA class I expression on viable human Langerhans cells and keratinocytes. Cytometry. 1996;26:260-264.
97. Gueniche A, Viac J, Lizard G, et al. Effect of nickel on the activation state of normal human keratinocytes through interieukin 1 and intercellular adhesion molecule 1 expression. Br J Dermatol. 1994;131:250-256.
98. Gueniche A, Viac J, Lizard G, et al. Effect of various metals on intercellular adhesion molecule-1 expression and tumour necrosis factor alpha production by normal human keratinocytes. Arch Dermatol Res. 1994;286:466-470.
99. Dang LH, Michalek MT, Takei F, et al. Role of ICAM-1 in antigen presentation demonstrated by ICAM-1 defective mutants. J Immunol. 1990; 144:4082-4091.
100. Piguet PF Keratinocyte-derived tumor necrosis factor and the physiopathology of the skin, Springer Semin Immunopathol. 1992;13:345-354.
101. Terunuma A, Aiba S, Tagami H. Cytokine mRNA profiles in cultured human skin component cells exposed to various chemicals: a simulation model of epicutaneous stimuli induced by skin barrier perturbation in comparison with that due to exposure to haptens or irritant. J Dermatol Sci. 2001;26:85-93.
102. Ansel J, Perry P, Brown J, et al. Cytokine modulation of keratinocyte cytokines. J Invest Dermatol. 1990;94:101S-107S.
103. Sebastiani S, Albanesi C, De PO, et al. The role of chemokines in allergic contact dermatitis. Arch Dermatol Res. 2002;293:552-559.
104. Albanesi C, Scarponi C, Giustizieri ML, et al. Keratinocytes in inflammatory skin diseases. Curr Drug Targets Inflamm Allergy. 2005;4329-334.
105. Cumberbatch M, Bhushan M, Dearman RJ, et al. IL-1beta-induced Langerhans' cell migration and TNF-alpha production in human skin: regulation by lactoferrin. Clin Exp Immunol. 2003;132:352-359. production in human skin: regulation by lactoferrin. Clin Exp Immunol. 2003;132:352-359.
106. Cumberbatch M, Dearman RJ, Griffiths CE, et al. Langerhans cell migration. Clin Exp Dermatol. 2000;25:413-418.
107. Cumberbatch M, Griffiths CE, Tucker SC, et al. Tumour necrosis factor-alpha induces Langerhans cell migration in humans. Br J Dermatol. 1999;141:192-200.
108. Nassif A, Moslehi H, Le Gouvello S, et al. Evaluation of the potential role of cytokines in toxic epidermal necrolysis. J Invest Dermatol. 2004; 123:850-855.
109. Hulette BA, Ryan CA, Gerberick GF. Elucidating changes in surface marker expression of dendritic cells following chemical allergen treatment. Toxicol Appl'Pharmacol. 2002;182:226-233.
110. Albanesi C, Cavani A, Girolomoni G. Interferon-gamma-stimulated human keratinocytes; express the genes necessary for the production of peptide-loaded MHC class II molecules. J Invest DermatoL 1998;110:138-142.
111. Basham TY, Nickoloff BJ, Merigan TC, et al. Recombinant gamma interferon induces HLA-DR expression on cultured human keratinocytes. J Invest Dermatol. 1984;83:88-90.
112. Lisby S, Muller KM, Jongeneel CV, et al. Nickel and skin irritants up-regulate tumor necrosis factor-alpha mRNA in keratinocytes by different but potentially synergistic mechanisms. Int Immunol. 1995;7:343-352.
113. Wilmer JL, Burleson FG, Kayama F, et al. Cytokine induction in human epidermal keratinocytes exposed to contact irritants and its relation to chemical-induced inflammation in mouse skin. J Invest DermatoL 1994;102:915-922.
114. Piguet PF, Grau GE, Hauser C, et al. Tumor necrosis factor is a critical mediator in hapten induced irritant and contact hypersensitivity reactions. J Exp Med. 1991;173:673-679.
115. Vandebriel RJ, Van Och FM, van Loveren H. In vitro assessment of sensitizing activity of low molecular weight compounds. Toxicol Appl Pharmacol. 2005;207:142-148.
116. O'Garra A, McEvoy LM, Zlotnik A. T-cell subsets: chemokine receptors guide the way. Curr Biol. 1998;8:R646-R649.
117. Lebrec H, Kerdine S, Gaspard I, et al. Th(1)Th(2) responses to drugs. Toxicology. 2001;158:25-29.
118. Umetsu DT, DeKruyff RH. Th1 and Th2 CD4+ cells in the pathogenesis of allergic diseases. Proc Soc Exp Biol Med. 1997;215.11-20.
119. Xu H, Dilulio NA, Fairchild RL. T cell populations primed by hapten sensitization in contact sensitivity are distinguished by polarized patterns of cytokine production: interferon gamma-producing (Tc1) effector CD8+ T cells and interleukin (11) 4/11-10-producing (Th2) negative regulatory CD4+ T cells. J Exp Med. 1996;183-1001-1012.
120. Fuchs J, Zollner TM, Kaufmann R, et al. Redox-modulated pathways in inflammatory skin diseases. Free Radic Biol Med. 2001;30:337-353.
121. 'Steinbrink K, Sorg C, Macher E. Low zone tolerance to contact allergens in mice: a functional role for CD8+ T helper type 2 cells. J Exp Med. 1996;183:759-768.
122. Dearman RJ, Basketter DA, Kimber I. Characterization of chemical allergens as a function of divergent cytokine secretion profiles induced in mice. Toxicol Appi Pharmacol. 1996;138.308-316.
123. Dieli F, Asherson GL, Sireci G, et al. Development of IFN-gamma-producing CD8+ gamma delta+ T lymphocytes and IL-2-producing CD4+ alpha beta+ T lymphocytes during contact sensitivity. J Immuno; 1997;158:2567-2575.
124. Blaise GA, Gauvin D, Gangal M, et al. Nitric oxide, cell signaling and cell death. Toxicology. 2005;208:177-192.
125. Ross R, Reske-Kunz AB. The role of NO in contact hypersensitivity. Int Immunopharmacol. 2001;1:1469-1478.
126. Bruch-Gerharz D, Ruzicka T, Kolb-Bachofen V. Nitric oxide in human skin: current status and future prospects. J Invest Dermatol 1998;110:1-7
127. Weller R. Nitric oxide: a key mediator in cutaneous physiology. Clin Exp Dermatol. 2003;28:511-514.
128. Deliconstantinos G, Villiotou V, Stravrides JC, Release by ultraviolet B (u.v.B) radiation of nitric oxide (NO) from human keratinocytes. a potential role for nitric oxide in erythema production. Br J Pharmacol. 1995; 114:1257-1265.
129. Nathan C. Inducible nitric oxide synthase: what difference does it make? J Clin Invest. 1997;100:2417-2423.
130. Arany I, Brysk MM, Brysk H, et al. Induction of iNOS mRNA by interferon-gamma in epithelial cells is associated with growth arrest and differentiation. Cancer Lett. 1996;110:93-96.
131. Qureshi AA, Hosoi J, Xu S, et al. Langerhans cells express inducible nitric oxide synthase and produce nitric oxide. J Invest Dermatol. 1996;107:815-821.
132. Rocha IM, Guillo LA. Lipopolysaccharide and cytokines induce nitric oxide synthase and produce nitric oxide in cultured normal human melanocytes. Arch Dermatol Res. 2001;293:245-248.
133. Chang HR, Tsao DA, Wang SR, et al. Expression of nitric oxide synthases in keratinocytes after UVB irradiation. Arch Dermatol Res. 2003;295:293-296.
134. Warren JB. Nitric oxide and human skin blood flow responses to acetylcholine and ultraviolet light. FASEB J. 1994;8:247-251.
135. Lerner LH, Qureshi AA, Reddy BV, et al. Nitric oxide synthase in toxic epidermal necrolysis and Stevens-Johnson syndrome. J Invest Dermatol. 2000;114:196-199.
136. Rowe A, Farrell AM, Bunker CB. Constitutive enclothelial and inducible nitric oxide synthase in inflammatory dermatoses. Br JDermatol. 1997;136:18-23.
137. Lippe IT, Stabentheiner A, Holzer P. Participation of nitric oxide in the mustard oil-induced neurogenic inflammation of the rat paw skin. Eur J Pharmacol. 1993;232:113-120.
138. Morita H, Hori M, Kitano Y. Modulation of picryl chloride-induced contact hypersensitivity reaction in mice by nitric oxide. J Invest Dermatol. 1996;107:549-552.
139. Ross R, Gillitzer C, Kleinz R, et al. Involvement of NO in contact hypersensitivity. Int Immunol. 1998;10:61-69.
140. Nathan C, Xie QW. Nitric oxide synthases: roles, tolls, and controls. Cell. 1994;78:915-918.
141. Forstermann U, Closs El, Pollock JS, et al. Nitric oxide synthase isozymes: characterization, purification, molecular cloning, and functions. Hypertension. 1994;23:1121-1131.
142. Wanikiat P, Woodward DF, Armstrong RA. Investigation of the role of nitric oxide and cyclic GMP in both the activation and inhibition of human neutrophils. Br J Pharmacol. 1997;122:1135-1145.
143. Shin WS, Hong YH, Peng HB, et al. Nitric oxide attenuates vascular smooth muscle cell activation by interferon-gamma: the role of constitutive NF-kappa B activity. J Biol Chem. 1996;271:11317-11324.
144. Bonham CA, Lu L, U Y, et al. Nitric oxide production by mouse bone marrow-derived dendritic cells: implications for the regulation of allogeneic T cell responses. Transplantation. 1996;62:1871-1877.
145. Lu L, Bonham CA, Chambers FG, et al. Induction of nitric oxide synthase in mouse dendritic cells by IFN-gamma, endotoxin, and interaction with allogeneic T cells: nitric oxide production is associated with dendritic cell apoptosis. J Immunol, 1996;157:3577-3586.
146. Virag L, Szabo E, Bakondi E, et al. Nitric oxide-peroxynitrite-poly(ADP-ribose) polymerase pathway in the skin. Exp Dermatol. 2002; 11: 189-202.
147. Briganti S, Picardo M. Antioxidant. activity, lipid peroxidation and skin diseases: what's new. J Eur Acad Dermatol Venereol. 2003;17:663-669.
148. Chain BM. Current issues in antigen presentation: focus on the dendritic cell. Immunol Lett. 2003;89:237-241.
149. Hubbard AK, Rothlein R. Intercellular adhesion molecule-1 (ICAM-1) expression and cell signaling cascades. Free Radid Biol Med. 2000;28:1379-1386.
150. Rutault K, Alderman C, Chain BM, et al. Reactive oxygen species activate human peripheral blood dendritic cells. Free Radic Biol Med. 1999;26:232-238. DOI: 10.1016/S0891-5849(98)00194-4
151. Verhasselt V, Goldman M, Willems F. Oxidative stress up-regulates IL-8 and TNF-alpha synthesis by human dendritic cells. Eur J Immunol. 1998;28:3886-3890.
152. Mates JM, Perez-Gomez C, Olalla L, et al. Allergy to drugs: antioxidant enzymic activities, lipid peroxidation and protein oxidative damage in human blood. Cell Biochem Funct 2000;18:77-84.
153. Coopman SA, Johnson RA, Platt R, et al. Cutaneous disease and drug reactions in HIV infection. N Engl J Med. 1993;328:1670-1674.
154. Buhl R, Jatte HA, Holroyd KJ, et al Systematic glutathione deficiency in symptom-free HIV-seropositive individuals. Lancet. 1989;2:1294-1298.
155. Kaur S, Zilmer M, Eisen M, et al. Patients with allergic and irritant contact dermatitis are characterized by striking change of iron and oxidized glutathione status in nonlesional area of the skin. J Invest Dermatol. 2001;116:886-890.
156. Kaur S, Zilmer M, Eisen M, et al. Nickel sulphate and epoxy resin: differences in iron status and glutathione redox ration at the time of patch testing. Arch Dermatol Res. 2004;295:517-520.
157. Nordberg J, Zhong L, Holmgren A, et al. Mammalian thioredoxin reductase is irreversibly inhibited by dinitrohalobenzenes by alkylation of both the redox active selenocysteine and its neighboring cysteine residue. J Biol Chem. 1998;273:10835-10842.
158. Vyas PM, Roychowdhury S, Woster PM, et al. Reactive oxygen species generation and its role in the differential cytotoxicity of the arylhydroxylamine metabolites of sulfamethoxazole and dapsone in normal human epidermal keratinocytes. Biochem Pharmacol. 2005;70:275-286.
159. Kantengwa S, Jornot L, Devenoges C, et al. Superoxide anions induce the maturation of human dendritic cells. Am J Respir Crit Care Med. 2003;167:431-437.
160. Chen KH, Reece LM, Leary JF. Mitochondrial glutathione modulates TNF-alpha-induced endothelial cell dysfunction. Free Radic Biol Med. 1999;27:100-109.
161. Ikeda M, Schroeder KK, Mosher LB, et al. Suppressive effect of antioxidants on intercellular adhesion molecule-1 (ICAM-1) expression in human epidermal keratinocytes. J Invest Dermatol. 1994;103:791-796.
162. Faruqi RM, Poptic EJ, Faruqi TR, et al. Distinct mechanisms for N-acetylcysteine inhibition of cytokine-induced E-selectin and VCAM-1 expression. Am J Physiol. 1997;273:H817-H826.
163. Matsue H, Edelbaum D, Shalhevet D, et al. Generation and function of reactive oxygen species in dendritic cells during antigen presentation. J ImmunoL 2003;171:3010-3018.
164. Sandstrom PA, Buttke TM. Autocrine production of extracellular catalase prevents apoptosis of the human CEM T-cell line in serum-free medium. Proc NatlAcad Sci USA. 1993;90:4708-4712.
165. Kannan K, Jain SK Oxidative stress and apoptosis, Pathophysiology. 2000;7-153-163.
166. Oaawa Y. Kobavashi T. Nishioka A. et al. Reactive oxvaen sDecies-producina site in hvdrogen peroxide induced apoptosis of human peripheral T cells: involvement of lysosomal membrane destabilization. Int J Mol Med. 2004;13:383-388.
167. Devadas S, Zaritskaya L, Rhee SG, et aL Discrete generation of superoxide and hydrogen peroxide by T cell receptor stimulation: selective regulation of mitogen-activated protein kinase activation and fas ligand expression. J Exp Med. 2002; 195:59-70.
168. Hildeman DA, Zhu Y, Mitchell TC, et al. Activated T cell death in vivo mediated by proapoptotic bcl-2 family member bim. Immunity. 2002;16:759-767.
169. Fuchs J, Packer L. Antioxidant protection from solar-simulated radiation-induced suppression of contact hypersensitivity to the recall antigen nickel sulfate in human skin. Free Radic Biol Med. 1999;27:422-427,
170. Pasche-Koo F, Arechalde A, Arrighi JF, et al. Effect of N-acetylcysteine, an inhibitor of tumor necrosis factor, on irritant contact dermatitis in the human. Curr Probl DermatoL 1995;23:198-206.