Inhibitors of tumor necrosis factor-alpha for treatment ofpsoriatic patients

Cite item


The article describes current concepts of the role of cytokines in the pathogenesis of inflammatory diseases. The authors describe
the biological action of tumor necrosis factor-alpha and its soluble receptors on body cells. They also provide data on the role
of tumor necrosis factor-alpha in the formation of skin and joint inflammatory affections at psoriasis. The authors substantiate
treatment of medium to severe forms of psoriasis with biological gene-engineered anti-cytokine drugs, and provide and their
comparative characteristics.

About the authors

L F Znamenskaya


L F Znamenskaya


  1. Andreakos E.T., Foxwell B.M., Brennan F.M., Maini R.N., Feldmann M. Cytokines and anticytokine biologicals in autoimmunity: present and future. Cytokine Growth Factor Rev. 2002; 13: 299-313.
  2. Авдеева Ж.И., Алпатова И.А., Медуницын Н.В. Препараты системы цитокинов / Авдеева Ж.И., Алпатова И.А., Медуницын Н.В. // Цитокины и воспаление. Санкт- Петербург 2002; 1: 2: 33.
  3. Abbas A.K., Lichtman A.H. Cellular and molecular immunology. Philadelphia 2003; 83-105.
  4. А.С. Симбирцев. Цитокины - медиаторы защитных реакций организма / Симбирцев А.С. Цитокины и воспаление. Санкт- Петербург 2002; 1: 2: 38-39.
  5. Uyemura K., Yamamura M., Fivenson D.F., et al. The cytokine network in lesional and lesion-free psoriatic skin is characterized by a Thelper type 1 cell-mediated response. J Invest Dermatol 1993; 101: 701-705.
  6. Abou-Raja S., Abou-Raja A., Helmii M. Serum levels ofsome proinflammatory cytokines (TNF-alpha, IL-6, IL-17, IL-18) in psoriasis and psoriatic arthritis: reliable disease severity and disease activity biomarkers? Ann Rheum Dis 2008; 67: 523.
  7. Goedkoop A.Y., Krann M.C., Teunissen M.B. M. et al. Early effects of tumor necrosis factor-α blokade on skin and synovial tissue in patients with active psoriasis and psoriatic arthritis. Ann Rhum Dis 2004; 63: 769-773.
  8. Albanesi C., De Pita O., Girolomoni G. Resident skin cells in psoriasis: a special look at the pathogenetic functions of keratinocytes. Clin Dermatol 2007; 25 (6): 581-588.
  9. Nickoloff B.J. The cytokine network of psoriasis. Arch Dermatol 1991; 127: 871-884.
  10. Murphy J.E., Robert C., Kupper T.S. Interleukin-1 and cutaneous inflammation: a crucial link between innate and acquired immunity. J Invest Dermatol 2000; 114: 602-608.
  11. Neuner P. et al. Increased IL-6 production by monocytes and keratinocytes in patients with psoriasis. J Invest Dermatol 1991; 97: 27-33.
  12. Barker J.N. et al. Marked synergism between tumor necrosis factoralpha and interferon-gamma in regulation of keratinocyte derived adhesion molecules and chemotactic factors. J Clin Invest 1990; 85: 605-608.
  13. Arend W.P., Dayer J.M. Inhibition of the production and effects of interleukin-1 and tumor necrosis factor alpha in rheumatoid arthritis. Arthritis Rheum 1995; 38: 151-160.
  14. Asadullah K., Sterry W., Volk H.D. Analysis of cytokine expression in dermatology. Arch Dermatol 2002; 138: 1189-1196.
  15. Borish L.C., Steinke J.W. Cytokines and chemokines. J Allergy Clin Immunol 2003; 111: 460-475.
  16. Gupta S., Gollapudi S. Molecular mechanisms of TNF-alpha-induced apoptosis in aging human T cell subsets. Int. J Biochem Cell Biol 2005; 37 (5): 1034-1042.
  17. Зайко Н.Н., Быця Ю.В. Патологическая физиология. М.: МЕДпресс-информ, 2004; 199.
  18. Haranaka K., Carswell E.A.,Williamson B.D., Prendergast J.S., Satomi N., Old L.J. Purification, characterization, and antitumor activity of nonrecombinant mouse tumor necrosis factor. Proc Natl Acad Sci USA 1986; 83: 3949-3953.
  19. Heim M.E., Siegmund R., Illiger H.J., Klee M., Rieche K., Berdel W.E., Edler L. (1990) Tumor necrosis factor in advanced colorectal cancer: a phase II study. A trial of the phase I/II study group of the Association for Medical Oncology of the German Cancer Society. Onkologie 1990; 13: 444-447.
  20. Lenk H., Tanneberger S., Muller U., Ebert J., Shiga T (1989) Phase II clinical trial of high-dose recombinant human tumor necrosis factor. Cancer Chemother Pharmacol 1989; 24: 391-392.
  21. Насонов Е.Л. Фактор некроза опухолей-альфа - новая мишень для противовоспалительной терапии ревматоидного артрита. Е.Л. Насонов РМЖ. М., 2000; 8: 17: 718-22.
  22. Malaguarnera L., Imbesi R., Di Rosa M., Scuto A., Castrogiovanni P., Messina A., Sanfilippo S. Action of prolactin, IFN-gamma, TNF-alpha and LPS on heme oxygenase-1 expression and VEGF release in human monocytes/macrophages. Int. Immunopharmacol 2005; 5 (9): 1458-1469.
  23. Tartaglia L.A., Ayres T.M., Wong G.H., Goeddel D.V. «A novel domain within the 55 kd TNF receptor signals cell death». Mol Cell Biol 1993; 74: 845-853.
  24. Beg A.A., Finco T.S., Nantermet P.V., Baldwin A.S. Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss I kBa: A mechanism for NF-kB activation. Mol Cell Biol 1993; 13: 3301- 3310.
  25. Loop T. Thiopental inhibits tumor necrosis factor alpha-induced activation of nuclear factor kappa B through suppression of kappa B kinase activity. Anesthesiology 2003; 99 (2): 360-367.
  26. Bazzoni F., Beutler B. Tumor necrosis factor ligand and receptor families. N Engl J Med 1996; 334 (26): 1717-1725.
  27. Cunha F.Q., Poole S., Lorenzetti B.B., Fereira S.H. The pivotal role of tumor necrosis factor alpha in the development of inflammatory hyperalgesia. Br J Pharmacol 1992; 107: 660-669.
  28. Banno T., Gazel A., Blumenberg M. Effects of tumor necrosis factor- alpha (TNF alpha) in epidermal keratinocytes revealed using global transcriptional profiling. J Biol Chem 2004; 279 (31): 32633- 32642.
  29. Yang L., Froio R.M., Sciuto T.E., Dvorak A.M., Alon R., Luscinskas F.W. ICAM-1 regulates neutrophil adhesion and transcellular migration of TNF-(alpha) activated vascular endothelium under flow. Blood 2005; 106: 584-589.
  30. Федоров С.М., Самсонов В.А., Селисский Г.Д. и др. Роль цитокинов в патогенезе дерматозов / С.М. Федоров, В.А. Самсонов, Г.Д. Селисский. Вестн. дерматол. 1997; 1: 16-18.
  31. Alvaro-Gracia J.M., Zvaifler N.J., Firestein G.S. Cytokines in chronoc inflammatory arthritis. V. Mutual antagonism between interferon-gamma and tumor necrosis factor-alpha on HLA-DR expression, prolipheration, collagenase production, and granulocyte macrophage coloby-stimulating factor production by rheumatoid arthritis synoviocytes. J Clin Invest 1880; 86: 1790-1798.
  32. Shingu M., Nagai Y., Isayama T., et al. The effects of cytokines on metalloproteinase inhibitors (TIMP) and collagenase production by human chondrocytes and TIMP production by synovial cells and endothelial cells. Clin Exp Immunol 1993; 94: 145-149.
  33. Bertolini D.R., Nedwin G.E., Bringman T.S, et al. Stimulation of bone resorbtion and inhibition of bone formation in vitro by human tumor necrosis factors. Nature 1986; 319: 516-518.
  34. Dayer J.M., Beutler B., Cerami A. Cachectin/tumor necrosis factor stimulate collagenase and prostaglandin E production by human synovial cells and dermal fibroblast. J Exp Med 1985; 162: 2163- 2168.
  35. Haworth C., Brennan D., Chantry D., et al. Expression of granulocyte- macrophage colony-stimulating factor in rheumatoid arthritis: regulation by tumor necrosis factor-α. Eur J Immunol 1991; 21: 2575-2579.
  36. Brennan F., Chantry D., Turner M., et al. Inhibitory effects of TNF-α antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet 1989; 2: 244-247.
  37. Carlson D.L., Willis M.S., White D.J., Horton J.W., Giroir B.P. Tumor necrosis factor - alphainduced caspase activation mediates endotoxin-related cardiac dysfunction. Crit Care Med 2005; 33 (5): 1021-1028.
  38. Brennan F., Browne K.A., Green P.A., et al. Reduction of serum matrix metalloproteinase 1 and matrix metalloproteinase 3 in rheumatoid arthritis patients following anti-tumor necrosis factor therapy. Br J Rheumatol 1997; 36: 643-650.
  39. Cunha F.Q., Poole S., Lorenzetti B.B., Fereira S.H. The pivotal role of tumor necrosis factor alpha in the development of inflammatory hyperalgesia. Br J Pharmacol 1992; 107: 660-669.
  40. Dinarello C., Cannon J., Wolff S., et al. Tumor necrosis factor is an endogenous pyrogen and induces production of interleukin 1. J Exp Med 1986; 163: 1433-1450.
  41. Lupia E., Montatrucchio G., Battaglia E., et al. Role of tumor necrosis factor-α and platelet-activating factor in neoangiogenesis induced by synovial fluids of patients with rheumatoid arthritis. Eur J Immunol 1996; 26: 1690-1694.
  42. Ahmadzadeh N., Shingu M., Nobunaga M. The effect of recombinant tumor necrosis factor-α on superoxide and metalloproteinase production by synovial cells and chondrocytes. Clin Exp Rheumatol 1990; 8: 387-391.
  43. Macnaul K.L., Chartain N., Lark M., etal. Differential effects of IL-1 and TNF alpha on the expression of stromelisin, collagenase and their inhibitor, TIMP, in rheumatoid human synovial fibroblasts. Matrix Suppl 1992; 1: 198-199.
  44. Carlson D.L., Willis M.S., White D.J., Horton J.W., Giroir B.P. Tumor necrosis factor - alphainduced caspase activation mediates endotoxin-related cardiac dysfunction. Crit Care Med 2005; 33 (5): 1021-1028.
  45. Tak P.P., Taylor P.C., Breedveld F.C., et al. Decrease in cellularity and expression of adhesion molecules by anti-tumor necrosis factor α monoclonal antibody treatment in patients with rheumatoid arthritis. Arthritis Rheum 1996; 39: 1077-1081.
  46. Taylor P., Chapman P., Elliot M., et al. Reduced granulocyte traffic and chemotactic gradient in rheumatoid joints following anti-TNFα therapy. Arthritis Rheum 1997; 40: 80.
  47. Perkins D.J., Clair E.W., Misukonis M.A., Weinberg J.B. Reduction of NOS2 overexpression in rheumatoid arthritis patients treated with anti-tumor necrosis factor α monoclonal antibody. Arthritis Rheum 1998; 41, 2205-2210.
  48. Rodriguez-Galan M.C., Bream J.H., Farr A., Young H.A. Synergistic effect of IL-2, IL-12, and IL-18 on thymocyte apoptosis and Th1/ Th2 cytokine expression. J Immunol 2005; 174 (5): 2796-2804.
  49. Alvaro-Gracia J.M., Zvaifler N.J., Firestein G.S. Cytokines in chronoc inflammatory arthritis. V. Mutual antagonism between interferon-gamma and tumor necrosis factor-alpha on HLA-DR expression, prolipheration, collagenase production, and granulocyte macrophage coloby-stimulating factor production by rheumatoid arthritis synoviocytes. J Clin Invest 1880; 86: 1790-1798.
  50. Saripalli Y.V., Gaspari A.A. Focus on: biologics that affect therapeutic agents in dermatology. J Drugs Dermatol 2005; 4 (2): 233-245.
  51. Singh R., Robinson D.B., El-Gabalawy H.S. Emerging biologic therapies in rheumatoid arthritis: cell targets and cytokines. Curr Opin Rheumatol 2005; 17 (3): 274-279.
  52. Duan H., Koga T., Kohda F., Hara H., Urabe K., Furue M. Interleukin- 8-positive neutrophils in psoriasis. J Dermatol Sci 2001; 26 (2): 119-124.
  53. Myers W., Opeola M., Gottlieb A.B. Common clinical features and disease mechanisms of psoriasis and psoriatic arthritis. Curr Rheumatol Rep 2004; 6 (4): 306-313.
  54. Hammerberg C., Arend W.P., Fisher G.J., Chan L.S., Berger A.E., Haskill J.S., Voorhees J.J., Cooper K.D. Interleukin-1 receptor antagonist in normal and psoriatic epidermis. J Clin Invest 1992; 90 (2): 571-583.
  55. Ritchlin C. T. The pathogenesis of psoriasis and psoriatic arthritis. New applications for TNF inhibition. Immunex, Philadelphia 2000; 9: 20.
  56. Austin L.M., Ozawa M., Kikuchi T. et al. The majority of epidermal T cells in Psoriasis vulgaris lesions can produce type 1 cytokines, interferon-gamma, interleukin-2, and tumor necrosis factor-αlpha, defining TC1 (cytotoxic T lymphocyte) and TH1 effector populations: a type 1 differentiation bias is also measured in circulating blood T cells in psoriatic patients. J Invest Dermatol 1999; 113 (5): 752-759.
  57. Bonifati C., Carducci M., Cordiali F.P. et al. Correlated increases of tumour necrosis factor-αlpha, interleukin-6 and granulocyte monocyte-colony stimulating factor levels in suction blister fluids and sera of psoriatic patients-relationships with disease severity. Clin Exp Dermatol 1994; 19 (5): 383-387.
  58. Шегай М.М., Кешилева З.Б., Акышбаева Г.А. Роль некоторых цитокинов в развитии псориаза. М.М. Шегай, З.Б. Кешилева, Г.А. Акышбаева. Вестн. дерматол. 1998; 5: 7-13.
  59. Uyemura K., Yamamura M., Fivenson D.F. et al. The cytokine network in lesional and lesion-free psoriatic skin is characterized by a T-helper type 1 cell-mediated response. J Invest Dermatol 1993; 101 (5): 701-705.
  60. Feldmann M., Maini R.N. Discovery of TNF-alpha as a therapeutic target in rheumatoid arthritis: preclinical and clinical studies. Joint Bone Spine 2002; 69: 12-18.
  61. Anandarajah A.P., Ritchlin C.T. Pathogenesis of psoriatic arthritis. Introduction to TNF/pathophysiology of TNF 7. Curr Opin Rheumatol 2004; 16 (4): 338-343.
  62. Ritchlin C.T. The pathogenesis of psoriatic arthritis. Сurr Opin Rheumatol 2005; 17: 406-412.
  63. Gately M.K., Renzetti L.M., Magram J., et al. The interleukin-12/ interleukin-12-receptor system: role in normal and pathologic immune responses. Ann Rev Immunol 1998; 16: 495-521. 65. Rizova Elena. Патофизиология псориаза, роль ИЛ 12/23 и новые подходы к лечению. Тезисы докладов. Х Всероссийский съезд дерматовенерологов. М., 2008; 35.
  64. Курдина М.И. Антицитокиновая терапия псориаза - шаг в будущее. М.И. Курдина. Фарматека: Междунар. мед. журн. 2004; 7: 59-65.
  65. Владимиров В.В. Современные методы лечения псориаза. В.В. Владимиров. Дерматология, приложение к журналу «Consilium Medicum» 2006; 5: 4.
  66. Granstein R.D. New treatments for psoriasis. N Engl J Med 2001; 345: 284-287.
  67. Feldmann M., Maini R.N. Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned? Ann Rev Immunol 2001; 19: 163-196. 70. Уэйт Гиббс. Нанотела. Уэйт Гиббс. В мире науки, 2005; 11: 45-46.
  68. Бадокин В.В. Перспективы применения ингибиторов ФНО - в терапии псориатического артрита. В.В. Бадокин. Клин. фармакол. и тер. 2005; 5-8.
  69. Antoni C., Manger B. Infliximab for psoriasis and psoriatic arthritis. Clin Exp Rheumatol 2002; 20 (28): 122-25.
  70. Winterfield L., Menter A. Psoriasis and its treatment with infliximabmediated tumor necrosis factor alpha blockade. Dermatol Clin 2004; 4: 437-447. 74. Инструкция по применению РЕМИКЕЙД № 01-11/89-07 от 15.05.2007; 13 c.
  71. Gottlieb A.B., Evans R., Li S. et al. Infliximab induction therapy for patients with severe plaque-type psoriasis: A randomized, doubleblind, placebo-controlled trial. J Am Acad Dermatol 2004; 51 (4): 534-42.
  72. Chaudhari U., Romano P., Mulcahy L.D., et al. Efficacy and safety of infliximab Monotherapy for plaque-type psoriasis: a randomized trial. Lancet 2001; 357: 1842.
  73. Singri P., West D.P., Gordon K.B. Biologic therapy for psoriasis: the new therapeutic frontier. Arch Dermatol 2002; 138: 657-63.
  74. Mendonca C.O., Burden A.D. Current concepts in psoriasis and its treatment. Pharmacol Ther 2003; 99: 133-147.
  75. Keystone E. Adalimumab therapy in rheumatoid arthritis. Rheum Dis Clin North Am 2004; 30 (2): 349-364. 80. Humira® (adalimumab) [package insert]. North Chicago. Abbott Laboratories, 2003.
  76. Weinblatt M.E., Keystone E.C., Furst D.E., Moreland L.W., Weisman M.H., Birbara C.A., Teoh L.A., Fischkoff S.A., Chartash E.K. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum 2003; 48: 35-45.
  77. Manger B., Lorenz H.M., Splekeler R. et al. Adalimumab (Humira) improves the signs and symptoms of joint, skin and nail manifestations of psoriatic arthritis (PsA): results from a German database of PsA patients reseiving adalimumab. Ann Rheum Dis 2008; 67: 528.
  78. Zaragoza V., Pérez A., Sánchez J.L., Oliver V., Martínez L., Alegre V. Long-term safety and efficacy of etanercept in the treatment of psoriasis. Actas Dermosifiliogr 2010; 101 (1): 47-53.
  79. Papp K.A. et al. A global phase III randomized controlled trial of etanercept in psoriasis: safety, efficacy, and effect of dose reduction. Br J Dermatol 2005; 152: 1304-1312.
  80. Leonardi C.L. et al. Etanercept as monotherapy in patients with psoriasis. N Engl J Med 2003; 349: 2014-2022.
  81. Sorbera L.A., Rabasseda X., Castaner R.M. Adalimumab: antiarthritic treatment of IBD. Drugs Future 2001; 26 (7): 639-646.
  82. Kohno T., Stevens S.R., Louie J.S. Adalimumab and infliximab bind to Fc-receptor and C1q and generate immunoprecipitation-A different mechanism from etanercept. J Am Acad Dermatol 2005; 52 (3): 400.
  83. Roskos L.K., Davis G.C., Schwab G.M. The clinical pharmacology of therapeutic monoclonal antibodies. Drug Development Research 2004; 61: 108-120.
  84. Brimhall A.K., King L.N., Licclardone J.C., et al. Safety and efficacy of alefacept, efalizumab, etanercept and infliximab in treating moderate to severe plaque psoriasis: a meta-analysis of randomized controlled trials. Br J Dermatol 2008; 159: 274-85.
  85. Schellekens H. Immunogenicity of therapeutic proteins: clinical implications and future prospects. Clin Ther 2002; 24 (11): 1720-1740.
  86. Dillman R.O. Human antimouse and antiglobulin response to monoclonal antibodies. Antibody Immunocon Radiopharm 1990; 3: 1-15.
  87. Anderson P.J. Tumor necrosis factor inhibitors: Clinical implications of their different immunogenicity profiles. Semin Arthritis Rheum 2005; 34: 19-22.
  88. Lobo E.D., Hansen R.J, Balthasar J.P. Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci 2004; 93 (11): 2645-2668.
  89. Moreland L.W. Soluble tumor necrosis factor receptor (p75) fusion protein (Enbrel) as a therapy for rheumatoid arthritis. Rheum Dis Clin 1998; 24: 579-591.
  90. Goldsmith D.R., Wagstaff A.J. Etanercept: a review of its use in the management of plaque psoriasis and psoriatic arthritis. Am J Clin Dermatol 2005; 6 (2): 121-136.
  91. Porter S. Human immune response to recombinant human proteins. J Pharm Sci 2001; 90: 1-11.
  92. Farrell R.J., Alsahli M., Jeen Y.T., Falchuk K.R., Peppercorn M.A., Michetti P. (2003) Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: a randomized controlled trial. Gastroenterology 2003; 124 (4): 917-924.
  93. Black R.A., Rauch C.T., Kozlosky C.J., Peschon J.J., Slack J.L., Wolfson M.F., Castner B.J., Stocking K.L., Reddy P., Srinivasan S., Nelson N., Boiani N., Schooley K.A., Gerhart M., Davis R., Fitzner J.N., Johnson R.S., Paxton R.J., March C.J., Cerretti D.P. (1997). «A metalloproteinase disintegrin that releases tumour-necrosis factor- alpha from cells». Nature 1997; 385: 729.
  94. Enbrel® (etanercept) [package insert]. Thousand Oaks, Calif. Amgen Inc. and Wyeth-Ayerst Pharmaceuticals 2004.

Copyright (c) 2010 Znamenskaya L.F., Znamenskaya L.F.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 60448 от 30.12.2014.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies