Journal of Clinical Immunology

, Volume 29, Issue 2, pp 210–214 | Cite as

Serum Levels of IL-17 and IL-22 Are Reduced by Etanercept, but not by Acitretin, in Patients with Psoriasis: a Randomized-Controlled Trial

  • M. Caproni
  • E. Antiga
  • L. Melani
  • W. Volpi
  • E. Del Bianco
  • P. Fabbri



There are no controlled trials comparing etanercept and acitretin efficacy and therapeutic mechanisms in psoriasis.

Materials and methods

In the present study, 30 patients were given etanercept 50 mg twice weekly and 30 patients acitretin 0.4 mg/kg per day, both for 12 weeks. Before and after treatment, psoriasis area and severity index was calculated, and serum levels of interleukin (IL)-17, IL-22, and IL-23 were investigated.


After treatment, psoriasis area and severity index was significantly lower for both groups. However, etanercept-treated patients showed lower psoriasis area and severity index than acitretin-treated ones. Psoriasis patients showed higher IL-17 and IL-22 levels than controls, while no IL-23 was found in any serum. Furthermore, a correlation between IL-17 levels and psoriasis severity was found. Only etanercept was able to reduce IL-17 and IL-22 levels.


Our findings suggest that etanercept is more effective than acitretin in the treatment of psoriasis and that it is able to affect Th17 system.


Psoriasis IL-17 IL-22 IL-23 etanercept 


  1. 1.
    Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature 2007;445:866–73. doi: 10.1038/nature05663.PubMedCrossRefGoogle Scholar
  2. 2.
    Boyman O, Conrad C, Tonel G, Gilliet M, Nestle FO. The pathogenic role of tissue-resident immune cells in psoriasis. Trends Immunol 2004;25:295–305. doi: 10.1016/ Scholar
  3. 3.
    Schlaak JF, Buslau M, Jochum W, Hermann E, Girndt M, Gallati H, et al. T cells involved in psoriasis vulgaris belong to the Th1 subset. J Invest Dermatol 1994;102:145–9. doi: 10.1111/1523-1747.ep12371752.PubMedCrossRefGoogle Scholar
  4. 4.
    Zaba LC, Cardinale I, Gilleaudeau P, Sullivan-Whalen M, Suárez Fariñas M, Fuentes-Duculan J, et al. Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses. J Exp Med 2007;204:3183–94. doi: 10.1084/jem.20071094.PubMedCrossRefGoogle Scholar
  5. 5.
    Boniface K, Guignouard E, Pedretti N, Garcia M, Delwail A, Bernard FX, et al. A role for T cell-derived interleukin 22 in psoriatic skin inflammation. Clin Exp Immunol 2007;150:407–15.PubMedGoogle Scholar
  6. 6.
    Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, Wu J, Ouyang W. Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 2007;445:648–51. doi: 10.1038/nature05505.PubMedCrossRefGoogle Scholar
  7. 7.
    Wolk K, Witte E, Wallace E, Döcke WD, Kunz S, Asadullah K, et al. IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur J Immunol 2006;36:1309–23. doi: 10.1002/eji.200535503.PubMedCrossRefGoogle Scholar
  8. 8.
    Piskin G, Sylva-Steenland RM, Bos JD, Teunissen MB. In vitro and in situ expression of IL-23 by keratinocytes in healthy skin and psoriasis lesions: enhanced expression in psoriatic skin. J Immunol 2006;176:1908–15.PubMedGoogle Scholar
  9. 9.
    Li J, Li D, Tan Z. The expression of interleukin-17, interferon-gamma, and macrophage inflammatory protein-3 alpha mRNA in patients with psoriasis vulgaris. J Huazhong Univ Sci Technolog Med Sci 2004;24:294–6.PubMedGoogle Scholar
  10. 10.
    Li J, Chen X, Liu Z, Yue Q, Liu H. Expression of Th17 cytokines in skin lesions of patients with psoriasis. J Huazhong Univ Sci Technolog Med Sci 2007;27:330–2. doi: 10.1007/s11596-007-0329-1.PubMedCrossRefGoogle Scholar
  11. 11.
    Lee E, Trepicchio WL, Oestreicher JL, Pittman D, Wang F, Chamian F, Dhodapkar M, Krueger JG. Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. J Exp Med 2004;199:125–30. doi: 10.1084/jem.20030451.PubMedCrossRefGoogle Scholar
  12. 12.
    Lowes MA, Kikuchi T, Fuentes-Duculan J, Cardinale I, Zaba LC, Haider AS, Bowman EP, Krueger JG. Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol 2008;128:1207–11. doi: 10.1038/sj.jid.5701213.PubMedCrossRefGoogle Scholar
  13. 13.
    Weaver CT, Hatton RD, Mangan PR, Harrington LE. IL-17 family cytokines and the expanding diversity of effector T cell linear. Annu Rev Immunol 2007;25:821–52. doi: 10.1146/annurev.immunol.25.022106.141557.PubMedCrossRefGoogle Scholar
  14. 14.
    Vanden-Eijnden S, Goriely S, De Wit D, Willems F, Goldman M. IL-23 up-regulates IL-10 and induces IL-17 synthesis by polyclonally activated naive T cells in human. Eur J Immunol 2005;35:469–75. doi: 10.1002/eji.200425677.PubMedCrossRefGoogle Scholar
  15. 15.
    Kikly K, Liu L, Na S, Sedgwick JD. The IL-23/Th17 axis: therapeutic targets for autoimmune inflammation. Curr Opin Immunol 2006;18:670–5. doi: 10.1016/j.coi.2006.09.008.PubMedCrossRefGoogle Scholar
  16. 16.
    Huber AK, Jacobson EM, Jazdzewski K, Concepcion ES, Tomer Y. IL-23R is a major susceptibility gene for Graves’ ophthalmopathy: the IL-23/Th17 axis extends to thyroid autoimmunity. J Clin Endocrinol Metab 2008;93:1077–81. doi: 10.1210/jc.2007-2190.PubMedCrossRefGoogle Scholar
  17. 17.
    Komiyama Y, Nakae S, Matsuki T, Nambu A, Ishigame H, Kakuta S, et al. IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis. J Immunol 2006;177:566–73.PubMedGoogle Scholar
  18. 18.
    Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B, et al. Phenotypic and functional features of human Th17 cells. J Exp Med 2007;204:1849–61. doi: 10.1084/jem.20070663.PubMedCrossRefGoogle Scholar
  19. 19.
    Chong BF, Wong HK. Immunobiologics in the treatment of psoriasis. Clin Immunol 2007;123:129–38. doi: 10.1016/j.clim.2007.01.006.PubMedCrossRefGoogle Scholar
  20. 20.
    Tan JK, Aphale A, Malaviya R, Sun Y, Gottlieb AB. Mechanisms of action of etanercept in psoriasis. J Investig Dermatol Symp Proc 2007;12:38–45. doi: 10.1038/sj.jidsymp.5650037.PubMedCrossRefGoogle Scholar
  21. 21.
    van de Kerkhof PCM. Update of retinoid therapy of psoriasis in: an update on the use of retinoids in dermatology. Dermatol Ther 2006;19:252–63. doi: 10.1111/j.1529-8019.2006.00082.x.PubMedCrossRefGoogle Scholar
  22. 22.
    Leon A, Nguyen A, Letsinger J, Koo J. An attempt to formulate an evidence-based strategy in the management of moderate-to-severe psoriasis: a review of the efficacy and safety of biologics and prebiologic options. Expert Opin Pharmacother 2007;8:617–32. doi: 10.1517/14656566.8.5.617.PubMedCrossRefGoogle Scholar
  23. 23.
    Arican O, Aral M, Sasmaz S, Ciragil P. Serum levels of TNF-alpha, IFN-gamma, IL-6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity. Mediators Inflamm 2005;2005:273–9. doi: 10.1155/MI.2005.273.PubMedCrossRefGoogle Scholar
  24. 24.
    Kao CY, Chen Y, Thai P, Wachi S, Huang F, Kim C, et al. IL-17 markedly up-regulates beta-defensin-2 expression in human airway epithelium via JAK and NF-kappa B signaling pathways. J Immunol 2004;173:3482–91.PubMedGoogle Scholar
  25. 25.
    Boniface K, Bernard FX, Garcia M, Gurney AL, Lecron JC, Morel F. IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes. J Immunol 2005;174:3695–702.PubMedGoogle Scholar
  26. 26.
    Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R. IL-22 increases the innate immunity of tissues. Immunity 2004;21:241–54. doi: 10.1016/j.immuni.2004.07.007.PubMedCrossRefGoogle Scholar
  27. 27.
    Fisher GJ, Voorhees JJ. Molecular mechanisms of retinoid actions in skin. FASEB J 1996;10:1002–13.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • M. Caproni
    • 1
  • E. Antiga
    • 1
  • L. Melani
    • 1
  • W. Volpi
    • 1
  • E. Del Bianco
    • 1
  • P. Fabbri
    • 1
  1. 1.Department of Dermatological SciencesUniversity of FlorenceFlorenceItaly

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