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Modern anti-cytokine therapy of autoimmune diseases

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Abstract

The emergence of genetically engineered biological agents opened new prospects in the treatment of autoimmune and inflammatory diseases. Cytokines responsible for regulation of a wide range of processes during development of the normal immune response are among the most successful therapeutic targets. Studies carried out in recent decades and accompanied by rapid development of biotechnology have promoted establishing in detail the role and place of cytokines in autoimmune and inflammatory pathologies. Nevertheless, mechanisms that underlie anti-cytokine therapy are still not fully understood. This review examines the role of such cytokines as TNF, IL-1, and IL-6 in the development of inflammatory processes and the action mechanisms of their inhibitors.

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References

  1. Carswell, E. A., Old, L. J., Kassel, R. L., Green, S., Fiore, N., and Williamson, B. (1975) An endotoxin serum factor that causes necrosis of tumor, Proc. Natl. Acad. Sci. USA, 72, 3666–3670.

    CAS  PubMed Central  PubMed  Google Scholar 

  2. Tracey, D., Klareskog, L., Sasso, E. H., Salfeld, J. G., and Tak, P. P. (2008) Tumor necrosis factor antagonist mechanisms of action: a comprehensive review, Pharmacol. Therap., 117, 244–279.

    CAS  Google Scholar 

  3. Black, R. A., Rauch, C. R., Kozlovsky, 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., and Cerretti, D. P. (1997) A metalloproteinase disintegrin that releases tumor-necrosis factor-alpha from cells, Nature, 385, 729–733.

    CAS  PubMed  Google Scholar 

  4. Simmonds, R. E., and Foxwell, B. M. (2008) NF-κB and its relevance to arthritis and inflammation, Rheumatology, 47, 584–590.

    CAS  PubMed  Google Scholar 

  5. Grell, M., Douni, E., Wajant, H., Lohden, M., Clauss, M., Maxeiner, B., Georgopoulus, S., Lesslauer, W., Kollias, G., Pfizenmaier, K., and Scheurich, P. (1995) The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor, Cell, 83, 793–802.

    CAS  PubMed  Google Scholar 

  6. Grell, M., Becke, F. M., Wajant, H., Mannel, D. N., and Scheurich, P. (1998) TNF receptor type 2 mediates thymocyte proliferation independently of TNF receptor type 1, Eur. J. Immunol., 28, 257–263.

    CAS  PubMed  Google Scholar 

  7. Carpentier, I., Coornaert, B., and Beyaert, R. (2004) Function and regulation of tumor necrosis factor receptor type 2, Curr. Med. Chem., 11, 2205–2212.

    CAS  PubMed  Google Scholar 

  8. Chen, X., Wu, X., Zhou, Q., Howard, O. M. Z., Netea, M. G., and Oppenheim, J. J. (2013) TNFR2 is critical for stabilization of the CD4+FoxP3+ regulatory T cell phenotype in the inflammatory environment, J. Immunol., 190, 1076–1084.

    CAS  PubMed Central  PubMed  Google Scholar 

  9. Redl, H., Schlag, G., Adolf, G. R., Natmessing, B., and Davies, J. (1995) Tumor necrosis factor (TNF)-dependent shedding of the p55 TNF receptor in a baboon model of bacteremia, Infect. Immun., 63, 297–300.

    CAS  PubMed Central  PubMed  Google Scholar 

  10. Aderka, D., Engelmann, H., Maor, Y., Brakebusch, C., and Wallach, D. (1992) Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors, J. Exp. Med., 175, 323–329.

    CAS  PubMed  Google Scholar 

  11. Keeton, R., Allie, N., Dambuza, I., Abel, B., Hsu, N.-J., Sebesho, B., Randall, P., Burger, P., Fick, E., Quesniaux, V. F. J., Ryffel, B., and Jacobs, M. (2014) Soluble TNFRp75 regulates host protective immunity against Mycobacterium tuberculosis, J. Clin. Invest., 124, 1537–1551.

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Schett, G. (2009) Osteoimmunology in rheumatic diseases, Arthr. Res. Therap., 11, 210–216.

    Google Scholar 

  13. Abu-Amer, Y., Erdmann, J., Kollias, G., Alexopoulou, L., Ross, P., and Teitelbaum, S. L. (2000) Tumor necrosis factor receptors types 1 and 2 differentially regulate osteoclastogenesis, J. Biol. Chem., 275, 27307–27310.

    CAS  PubMed  Google Scholar 

  14. Requeiro, M., Kip, K. E., Baidoo, L., Swoqer, J. M., and Schraut, W. (2014) Postoperative therapy with infliximab prevents long-term Crohn’s disease recurrence, Clin. Gastroenterol. Hepatol., 12, 1494–1502.

    Google Scholar 

  15. Verazza, S., Negro, G., Marafon, D., Consolaro, A., Martini, A., and Ravelli, A. (2013) Possible discontinuation of therapies after clinical remission in juvenile idiopathic arthritis, Clin. Exp. Rheumatol., 31, S98–101.

    PubMed  Google Scholar 

  16. Huang, Z., Yang, B., Shi, Y., Cai, B., Li, Y., Feng, W., Fu, Y., Luo, L., and Wang, L. (2012) Anti-TNF-α therapy improves Treg and suppresses Teff in patients with rheumatoid arthritis, Cell. Immunol., 279, 25–29.

    CAS  PubMed  Google Scholar 

  17. Tanaka, Y., Hirata, S., Kubo, S., Fukuyo, S., Hanami, K., Sawamukai, N., Nakano, K., Nakayamada, S., Yamaoka, K., Sawamura, F., and Saito, K. (2013) Discontinuation of adalimumab after achieving remission in patients with established rheumatoid arthritis: 1 year outcome of the HONOR study, Ann. Rheum. Dis., 2013, Nov 28, doi: 10.1136/annrheumdis-2013-204016.

  18. Targan, S. R., Hanauer, S. B., Van Deventer, S. J., Mayer, L., Present, D. H., Braakman, T., DeWoody, K. L., Schaible, T. F., and Rutgeerts, P. J. (1997) A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease. Crohn’s disease cA2 study group, N. Engl. J. Med., 337, 1029–1035.

    CAS  PubMed  Google Scholar 

  19. Van Dullemen, H. M., Van Deventer, S. J., Hommes, D. W., Bijl, H. A., Jansen, J., Tytgat, G. N., and Woody, J. (1995) Treatment of Crohn’s disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2), Gastroenterology, 109, 129–135.

    PubMed  Google Scholar 

  20. Braun, J., Brandt, J., Listing, J., Zink, A., Alten, R., Golder, W., Gromnica-Ihle, E., Kellner, H., Krause, H., Schneider, M., Sorensen, H., Zeidler, H., Thriene, W., and Sieper, J. (2002) Treatment of active ankylosing spondylitis with infliximab: a randomized controlled multicentre trial, Lancet, 359, 1187–1193.

    CAS  PubMed  Google Scholar 

  21. Kruithof, E., Van den Bosch, F., Baeten, D., Herssens, A., De Keyser, F., Mielants, H., and Veys, E. M. (2002) Repeated infusion of infliximab, a chimeric anti-TNF-alpha monoclonal antibody, in patients with active spondyloarthropathy: one years follow up, Ann. Rheum. Dis., 61, 207–212.

    CAS  PubMed Central  PubMed  Google Scholar 

  22. Chaudhari, U., Romano, P., Mulcahy, L. D., Dooley, L. T., Baker, D. G., and Gottlieb, A. B. (2001) Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: randomized trial, Lancet, 357, 1842–1847.

    CAS  PubMed  Google Scholar 

  23. Knight, D. M., Trinh, H., Le, J., Siegel, S., Shealy, D., McDonough, M., Scallon, B., Moore, M. A., Vilcek, J., and Daddona, P. (1993) Construction and initial characterization of a mouse-human chimeric anti-TNF antibody, Mol. Immunol., 30, 1143–1453.

    Google Scholar 

  24. Scallon, B. J., Moore, M. A., Trinh, H., Knight, D. M., and Ghrayeb, J. (1995) Chimeric anti-TNF-alpha monoclonal antibody cA2 binds recombinant transmembrane TNF-alpha and activates immune effector functions, Cytokine, 7, 251–259.

    CAS  PubMed  Google Scholar 

  25. Kruglov, A. A., Grivennikov, S. I., Kuprash, D. V., Winsauer, C., Prepens, S., Seleznik, G. M., Ebert, G., Littman, D. R., Heikenwalder, M., Tumanov, A. V., and Nedospasov, S. A. (2013) Nonredundant function of soluble LTa3 produced by innate lymphoid cells in intestinal homeostasis, Science, 342, 1243–1246.

    CAS  PubMed  Google Scholar 

  26. Lukina, G. V., and Sigidin, Ya. A. (2008) Safety of therapy with adalimumab, Nauch. Prakt. Revmatol., 2, 60–63.

    Google Scholar 

  27. Sigidin, Ya. A., and Lukina, G. V. (2008) Adalimumab in therapy of early rheumatoid arthritis, Nauch. Prakt. Revmatol., 2, 56–59.

    Google Scholar 

  28. Kay, J., and Rahman, U. (2009) Golimumab: a novel human anti-TNF-α monoclonal antibody for the treatment of rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis, Core Evidence, 4, 159–170.

    CAS  PubMed Central  Google Scholar 

  29. Lukina, G. V., and Sigidin, Ya. A. (2012) Certolizumab in therapy of rheumatoid arthritis, Sovrem. Revmatol., 2, 44–49.

    Google Scholar 

  30. Shealy, D., Cai, A., Staquet, K., Baker, A., Lacy, E. R., Johns, L., Vafa, O., Gunn III, G., Tam, S., Sague, S., Wang, D., Brigham-Burke, M., Dalmonte, P., Emmell, E., Pikounis, B., Bugelski, P. J., Zhou, H., Scallon, B., and Giles-Komar, J. (2010) Characterization of golimumab, a human monoclonal antibody specific for human tumor necrosis factor α, MAbs, 2, 428–439.

    PubMed Central  PubMed  Google Scholar 

  31. Schaible, H.-G., Von Anchet, G. S., Boettger, M. K., Brauer, R., Gajda, M., Richter, F., Hensellek, S., Brenn, D., and Natura, G. (2010) The role of proinflammatory cytokines in the generation and maintenance of joint pain, Ann. NY Acad. Sci., 1193, 60–69.

    CAS  PubMed  Google Scholar 

  32. Notley, C. A., Inglis, J. J., Alzabin, S., McCann, F. E., McNamee, K. E., and Williams, R. O. (2008) Blockade of tumor necrosis factor in collagen-induced arthritis reveals a novel immunoregulatory pathway for Th1 and Th17 cells, J. Exp. Med., 205, 2491–2497.

    CAS  PubMed Central  PubMed  Google Scholar 

  33. Szalay, B., Vasarhelyi, B., Cseh, A., Tulassay, T., Deak, M., Kovacs, L., and Balog, A. (2013) The impact of conventional DMARD and biological therapies on CD4+ cell subsets in rheumatoid arthritis: a follow up study, Clin. Rheumatol., 33, 175–185.

    PubMed  Google Scholar 

  34. Evans, H. G., Roostalu, U., Walter, G. J., Gullick, N. J., Frederiksen, K. S., Roberts, C. A., Sumner, J., Baeten, D. L., Gerwien, J. G., Cope, A. P., Geissmann, F., Kirkham, B. W., and Taams, L. S. (2014) TNF-α blockade induces IL-10 expression in human CD4+ T cells, Nat. Commun., 5, 3199–3211.

    PubMed Central  PubMed  Google Scholar 

  35. Anolik, J. H., Ravikumar, R., Barnard, J., Owen, T., Almudevar, A., Milner, E. C., Miller, C. H., Dutcher, P. O., Hadley, J. A., and Sanz, I. (2008) Cutting edge: anti-tumor necrosis factor therapy in rheumatoid arthritis inhibits memory B lymphocytes via effects on lymphoid germinal centers and follicular dendritic cell networks, J. Immunol., 180, 688–692.

    CAS  PubMed  Google Scholar 

  36. Valencia, X., Stephens, G., Goldbach-Mansky, R., Wilson, M., Shevach, E. M., and Lipsky, P. E. (2006) TNF down-modulates the function of human CD4+ CD25hi T-regulatory cells, Blood, 108, 253–261.

    CAS  PubMed Central  PubMed  Google Scholar 

  37. Nie, H., Zheng, Y., Li, R., Cuo, T. B., He, D., Fang, L., Liu, X., Xiao, L., Chen, X., Wan, B., Chin, Y. E., and Zhang, J. Z. (2013) Phosphorylation of FOXP3 controls regulatory T cell function and is inhibited by TNF-α in rheumatoid arthritis, Nat. Med., 19, 322–328.

    CAS  PubMed  Google Scholar 

  38. Dinarello, C. A. (1994) The interleukin-1 family: 10 years of discovery, FASEB J., 8, 1314–1325.

    CAS  PubMed  Google Scholar 

  39. Arend, W. P., Malyak, M., Guthridge, C. J., and Gabay, C. (1998) Interleukin-1 receptor antagonist: role in biology, Ann. Rev. Immunol., 16, 27–55.

    CAS  Google Scholar 

  40. Magne, D., Palmer, G., Barton, J. L., Mezin, F., Talabot-Ayer, D., Bas, S., Duffy, T., Noger, M., Guerne, P.-A., Nicklin, M. J. H., and Gabay, C. (2006) The new IL-1 family member IL-1F8 stimulates production of inflammatory mediators by synovial fibroblast and articular, Arthr. Res. Ther., 8, R80.

    Google Scholar 

  41. Kumar, S., McDonnell, P. C., Lehr, R., Tierney, L., Tzimas, M. N., Griswold, D. E., Capper, E. A., Tal-Singer, R., Wells, G. I., Doyle, M. L., and Young, P. R. (2000) Identification and initial characterization of four novel members of the interleukin-1 family, J. Biol. Chem., 275, 10308–10314.

    CAS  PubMed  Google Scholar 

  42. Smith, D. E., Renshaw, B. R., Ketchem, R. R., Kubin, M., Garka, K. E., and Sims, J. E. (2001) Four new members expand the interleukin-1 family, J. Biol. Chem., 275, 1169–1175.

    Google Scholar 

  43. Dinarello, C. A. (1996) Biologic basis for interleukin-1 in disease, Blood, 87, 2095–2147.

    CAS  PubMed  Google Scholar 

  44. Sims, J. E., and Smith, D. E. (2010) The IL-1 family: regulators of immunity, Nat. Rev. Immunol., 10, 89–102.

    CAS  PubMed  Google Scholar 

  45. O’Neill, L. A. J. (2008) The interleukin-1 receptor/Toll-like receptor superfamily: 10 years of progress, Immunol. Rev., 226, 10–18.

    PubMed  Google Scholar 

  46. Garlanda, C., Dinarello, C. A., and Mantovani, A. (2013) The interleukin-1 family: back to the future, Immunity, 39, 1003–1018.

    CAS  PubMed  Google Scholar 

  47. Martinon, F., Mayor, A., and Tschopp, J. (2009) The inflammasomes: guardians of the body, Ann. Rev. Immunol., 27, 229–269.

    CAS  Google Scholar 

  48. Gross, O., Yazdi, A. S., Thomas, C. J., Masin, M., Heinz, L. X., Guarda, G., Quadroni, M., Drexler, S. K., and Tschopp, J. (2012) Inflammasome activators induce interleukin-1α secretion via distinct pathways with differential requirement for the protease function of caspase-1, Immunity, 36, 388–400.

    CAS  PubMed  Google Scholar 

  49. Colotta, F., Re, F., Muzio, M., Bertini, R., Polentarutti, N., Sironi, M., Giri, J. G., Dower, S. K., Sims, J. E., and Mantovani, A. (1993) Interleukin-1 type II receptor: a decoy target for IL-1 that is regulated by IL-4, Science, 261, 472–475.

    CAS  PubMed  Google Scholar 

  50. Colotta, F., Dower, S. K., Sims, J. E., and Mantovani, A. (1994) The type II “decoy” receptor: a novel regulatory pathway for interleukin 1, Immunol. Today, 15, 562–528.

    CAS  PubMed  Google Scholar 

  51. Penton-Rol, G., Orlando, S., Polentarytti, N., Bernasconi, S., Muzio, M., Introna, M., and Mantovani, A. (1999) Bacterial lipopolysaccharide causes rapid shedding, followed by inhibition of mRNA expression, of the IL-1 type II receptor, with concomitant up-regulation of the type I receptor and induction of incompletely spliced transcript, J. Immunol., 162, 2931–2938.

    CAS  PubMed  Google Scholar 

  52. Barksby, H. E., Lea, S. R., and Preshaw, P. M. (2007) The expanding family of interleukin-1 cytokines and their role in destructive inflammatory disorders, Clin. Exp. Immunol., 149, 217–225.

    CAS  PubMed Central  PubMed  Google Scholar 

  53. Smith, D. E., Hanna, R., Friend, D., Moore, H., Chen, H., Farese, A. M., MacVittie, T. J., Virca, G. D., and Sims, J. E. (2003) The soluble form of IL-1 receptor accessory protein enhances the ability of soluble type II IL-1 receptor to inhibit IL-1 action, Immunity, 18, 87–96.

    CAS  PubMed  Google Scholar 

  54. Donath, M. Y. (2014) Targeting inflammation in the treatment of type 2 diabetes: time to start, Nature Rev. Drug Discov., 13, 465–476.

    CAS  Google Scholar 

  55. Dinarello, C. A., and van der Meer, J. W. M. (2013) Treating inflammation by blocking interleukin-1 in humans, Semin. Immunol., 25, 469–484.

    CAS  PubMed  Google Scholar 

  56. Khanna, P., Gladue, H. S., Singh, M. K., FitzGerald, D., Bae, S., Prakash, S., Kaldas, M., Gogia, M., Berrocal, V., Townsend, W., Terkeltaub, R., and Khanna, D. (2014) Treatment of acute gout: a systematic review, Sem. Arthritis Rheum., 44, 31–38.

    CAS  Google Scholar 

  57. Sterba, G., and Sterba, Y. (2013) Controlling inflammation. Contemporary treatment for autoinflammatory diseases and syndromes, Dermatol. Clin., 31, 507–511.

    CAS  PubMed  Google Scholar 

  58. Gabay, C., and Arend, W. P. (1998) Treatment of rheumatoid arthritis with IL-1 inhibitors, Springer Semin. Immunopathol., 20, 229–246.

    CAS  PubMed  Google Scholar 

  59. Bunning, R. A., Richardson, H. J., Crawford, A., Skiodt, H., Hughes, D., Evans, D. B., Gowen, M., Dobson, P. R., Brown, B. L., and Russell, R. (1986) The effect of interleukin-1 on connective tissue metabolism and its relevance to arthritis, Agents Actions Suppl., 18, 131–152.

    CAS  PubMed  Google Scholar 

  60. Volin, M. V., Shah, M. R., Tokuhira, M., Haines, G. K., Woods, J. M., and Koch, A. E. (1998) RANTES expression and contribution to monocyte chemotaxis in arthritis, Clin. Immunol. Immunopathol., 89, 44–53.

    CAS  PubMed  Google Scholar 

  61. Nakatsuka, K., Tanaka, Y., Hubscher, S., Abe, M., Wake, A., Saito, K., Morimoto, I., and Eto, S. (1997) Rheumatoid synovial fibroblasts are stimulated by the cellular adhesion to T cells through lymphocyte function associated antigen-1/intercellular adhesion molecule-1, J. Rheumatol., 24, 458–464.

    CAS  PubMed  Google Scholar 

  62. Garcia-Hernandez, M. H., Gonzalez-Amaro, R., and Portales-Perez, D. P. (2014) Specific therapy to regulate inflammation in rheumatoid arthritis: molecular aspects, Immunotherapy, 6, 623–636.

    CAS  PubMed  Google Scholar 

  63. Arend, W. P., and Gabay, C. (2004) Cytokines in the rheumatic diseases, Rheum. Dis. Clin. N. Am., 30, 41–67.

    Google Scholar 

  64. Chandrasekhar, S., and Phadke, K. (1988) Interleukin-1-induced alterations in proteoglycan metabolism and matrix assembly, Arch. Biochem. Biophys., 265, 294–301.

    CAS  PubMed  Google Scholar 

  65. Murata, M., Bonassar, L. J., Wright, M., Mankin, H. J., and Towle, C. A. (2003) A role for the interleukin-1 receptor in the pathway linking static mechanical compression to decreased proteoglycan synthesis in surface articular cartilage, Arch. Biochem. Biophys., 413, 229–235.

    CAS  PubMed  Google Scholar 

  66. Ikeda, S., Saijo, S., Murayama, M. A., Shimizu, K., Akitsu, A., and Iwakura, Y. (2014) Excess IL-1 signaling enhances the development of Th17 cells by down-regulating TGF-β-induced Foxp3 expression, J. Immunol., 192, 1449–1458.

    CAS  PubMed  Google Scholar 

  67. Brennan, F. M., and McInnes, I. B. (2008) Evidence that cytokines play a role in rheumatoid arthritis, J. Clin. Invest., 118, 3537–3545.

    CAS  PubMed Central  PubMed  Google Scholar 

  68. Opal, S. M., Fisher, C. J., Dhainaut, J. F., Vincent, J. L., Brase, R., Lowry, S. F., Sadoff, J. C., Slotman, G. J., Levy, H., Balk, R. A., Shelly, M. P., Pribble, J. P., LaBrecque, J. F., Lookabaugh, J., Donovan, H., Dubin, H., Baughman, R., Noeman, J., DeMaria, E., Matzek, K., Abraham, E., and Seneff, M. (1997) Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. The Interleukin-1 Receptor Antagonist Sepsis Investigator Group, Crit. Care Med., 25, 1115–1124.

    CAS  PubMed  Google Scholar 

  69. Fisher, C. J., Dhainaut, J. F., Opal, S. M., Pribble, J. P., Balk, R. A., Slotman, G. J., Iberti, T. J., Rackow, E. C., Shapiro, M., and Greenman, R. L. (1994) Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group, JAMA, 271, 1836–1843.

    PubMed  Google Scholar 

  70. Hirano, T., Yasukawa, K., Harada, H., Taga, T., Watanabe, Y., Matsuda, T., Kashiwamura, S., Nakajima, K., Koyama, K., Iwamatsu, A., Tsunasawa, S., Sakiyama, F., Matsu, H., Takahara, Y., Taniguchi, T., and Kishimoto, T. (1986) Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin, Nature, 324, 73–76.

    CAS  PubMed  Google Scholar 

  71. Rose-John, S. (2012) IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6, Int. J. Biol. Sci., 8, 1237–1247.

    CAS  PubMed Central  PubMed  Google Scholar 

  72. White, U. A., and Stephens, J. M. (2011) The gp130 receptor cytokine family: regulators of adipocyte development and function, Curr. Pharm. Des., 17, 340–346.

    CAS  PubMed Central  PubMed  Google Scholar 

  73. Kishimoto, J., Akira, S., and Taga, T. (1992) IL-6 receptor mechanism of signal transduction, Int. J. Immunopharmacol., 14, 431–438.

    CAS  PubMed  Google Scholar 

  74. Heinrich, P. C., Behrmann, I., Muller-Newen, G., Schaper, F., and Graeve, L. (1998) Interleukin-6-type cytokine signaling through the gp130/JAK/STAT pathway, Biochem. J., 334, 297–314.

    CAS  PubMed Central  PubMed  Google Scholar 

  75. Mullberg, J., Schooltink, H., Stoyan, T., Gunther, M., Graeve, L., Buse, G., Mackiewicz, A., Heinrich, P. C., and Rose-John, S. (1993) The soluble interleukin-6 receptor is generated by shedding, Eur. J. Immunol., 23, 473–480.

    CAS  PubMed  Google Scholar 

  76. Hurst, S. M., Wilkinson, T. S., McLoughlin, R. M., Jones, S., Horiuchi, S., Yamamoto, N., Rose-John, S., Fuller, G. M., Topley, N., and Jones, S. A. (2001) IL-6 and its soluble receptor orchestrate a temporal switch in the pattern of leukocyte recruitment seen during acute inflammation, Immunity, 14, 706–714.

    Google Scholar 

  77. Horiuchi, S., Koyanagi, Y., Miyamoto, H., Tanaka, Y., and Waki, M. (1994) Soluble interleukin-6 receptors released from T cell or granulocyte/macrophage cell lines and human peripheral blood mononuclear cells are generated through an alternative splicing mechanism, Eur. J. Immunol., 24, 1945–1948.

    CAS  PubMed  Google Scholar 

  78. Briso, E. M., Dienz, O., and Rincon, M. (2008) Cutting edge: soluble IL-6R is produced by IL-6R ectodomain shedding activates CD4 T cell, J. Immunol., 180, 7102–7106.

    CAS  PubMed Central  PubMed  Google Scholar 

  79. Lotz, M., Jirik, F., Kabouridis, P., Tsoukas, C., Hirano, T., Kishimoto, T., and Carson, D. A. (1988) B cell stimulating factor 2/interleukin 6 is a costimulant for human thymocytes and T lymphocytes, J. Exp. Med., 167, 1253–1258.

    CAS  PubMed  Google Scholar 

  80. Sehgal, P. B. (1990) Interleukin-6: molecular pathophysiology, J. Invest. Dermatol., 94, 2S–6S.

    CAS  PubMed  Google Scholar 

  81. Hirano, T. (1998) Interleukin 6 and its receptor: ten years later, Int. Rev. Immunol., 16, 249–284.

    CAS  PubMed  Google Scholar 

  82. Striz, I., Brabcova, E., Kolesar, L., and Sekerkova, A. (2014) Cytokine networking of innate immunity cells: a potential target of therapy, Clin. Sci., 126, 593–612.

    CAS  PubMed  Google Scholar 

  83. Marz, P., Cheng, J.-G., Gadient, R. A., Patterson, P. H., Stoyan, T., Otten, U., and Rose-John, S. (1998) Sympathetic neurons can produce and respond to interleukin 6, Proc. Natl. Acad. Sci. USA, 95, 3251–3256.

    CAS  PubMed Central  PubMed  Google Scholar 

  84. Streit, W. J., Hurley, S. D., McGraw, T. S., and Semple-Rowland, S. L. (2000) Comparative evaluation of cytokine profiles and reactive gliosis supports a critical role from interleukin-6 in neuroglia signaling during regeneration, J. Neurosci. Res., 61, 10–20.

    CAS  PubMed  Google Scholar 

  85. Wallenius, V., Wallenius, K., Ahren, B., Rudling, M., Carlsten, H., Dickson, S. L., Ohlsson, C., and Jansson, J. O. (2002) Interleukin-6-deficient mice develop mature-onset obesity, Nature Med., 8, 75–79.

    CAS  PubMed  Google Scholar 

  86. Erta, M., Quintana, A., and Hidalgo, J. (2012) Interleukin-6, major cytokine in the central nervous system, Int. J. Biol. Sci., 8, 1254–1266.

    CAS  PubMed Central  PubMed  Google Scholar 

  87. Scheller, J., Garbers, C., and Rose-John, S. (2014) Interleukin-6: from basic to selective blockade of pro-inflammatory activities, Semin. Immunol., 26, 2–12.

    CAS  PubMed  Google Scholar 

  88. Tanaka, T., and Kishimoto, T. (2012) Targeting interleukin-6: all the way to treat autoimmune and inflammatory disease, Int. J. Biol. Sci., 8, 1227–1236.

    CAS  PubMed Central  PubMed  Google Scholar 

  89. Kimura, A., and Kishimoto, T. (2010) IL-6: regulator of Treg/Th17 balance, Eur. J. Immunol., 40, 1830–1835.

    CAS  PubMed  Google Scholar 

  90. Samson, M., Audia, S., Janikashvili, N., Ciudad, M., Trad, M., Fraszczak, J., Ornetti, P., Maillefert, J. F., Miossec, P., and Bonnotte, B. (2012) Brief report: inhibition of interleukin-6 function corrects TH17/Treg cell imbalance in patients with rheumatoid arthritis, Arthritis Rheum., 64, 2499–24503.

    CAS  PubMed  Google Scholar 

  91. Nishida, S., Haqihara, K., Shima, Y., Kawai, M., Kuwahara, Y., Arimitsu, J., Hirano, T., Narazaki, M., Ogata, A., Yoshizaki, K., Kawase, I., Kishimoto, T., and Tanaka, T. (2009) Rapid improvement of AA amyloidosis with humanized anti-interleukin 6 receptor antibody treatment, Ann. Rheum. Dis., 68, 1235–1236.

    CAS  PubMed  Google Scholar 

  92. Roll, P., Muhammad, K., Schumann, M., Kleinert, S., Einsele, H., Dorner, T., and Tony, H. P. (2011) In vivo effect of the anti-interleukin-6 receptor tocilizumab on the B cell compartment, Arthritis Rheum., 63, 1255–1264.

    CAS  PubMed  Google Scholar 

  93. Thiolat, A., Semerano, L., Pers, Y. M., Biton, J., Lemeiter, D., Portales, P., Quentin, J., Jorgensen, C., Decker, P., Boissier, M. C., Louis-Plence, P., and Bessis, N. (2014) Interleukin-6 receptor blockade enhances CD39+ regulatory T cell development in rheumatoid arthritis and in experimental arthritis, Arthritis Rheum., 66, 273–283.

    CAS  Google Scholar 

  94. Tanaka, T., Hishitani, Y., and Ogata, A. (2014) Monoclonal antibodies in rheumatoid arthritis: comparative effectiveness of tocilizumab with tumor necrosis factor inhibitors, Biologics: Targets Therapy, 8, 141–153.

    Google Scholar 

  95. Tanaka, Y., and Mola, E. M. (2014) IL-6 targeting compared to TNF targeting in rheumatoid arthritis: studies of olokizumab, sarilumab and sirukumab, Ann. Rheum. Dis., 73, 1595–1597.

    CAS  PubMed  Google Scholar 

  96. Kallen, K.-J. (2002) The role of trans-signaling via the agonistic soluble IL-6 receptor in human disease, Biochim. Biophys. Acta, 1592, 323–343.

    CAS  PubMed  Google Scholar 

  97. Chalaris, A., Schmidt-Arras, D., Yamamoto, K., and Rose-John, S. (2012) Interleukin-6 trans-signaling and colonic cancer associated with inflammatory bowel disease, Digest. Dis., 30, 492–499.

    Google Scholar 

  98. Barkhausen, T., Tschernig, T., Rosenstiel, T., van Griensven, M., Vonberg, R.-P., Dorsch, M., Mueller-Heine, A., Chalaris, A., Scheller, J., Rose-John, S., Seegert, D., Krettek, C., and Waetzig, G. (2011) Selective blockade of interleukin-6 trans-signaling improves survival in a murine polymicrobial sepsis model, Crit. Care Med., 39, 1407–1413.

    CAS  PubMed  Google Scholar 

  99. Nowell, M. A., Williams, A. S., Carty, S. A., Scheller, J., Hayes, A. J., Jones, G. W., Richards, P. J., Slinn, S., Ernst, M., Jemkins, B. J., Topley, N., Rose-John, S., and Jones, S. A. (2009) Therapeutic targeting of IL-6 trans-signaling counteracts STAT3 control of experimental inflammatory arthritis, J. Immunol., 182, 613–622.

    CAS  PubMed  Google Scholar 

  100. Atreys, R., Mudter, J., Finotto, S., Mullberg, J., Jostock, T., Wirtz, S., Schutz, M., Bartsch, B., Holtmann, M., Becker, C., Strand, D., Czaja, J., Schlaak, J. F., Lehr, Y. A., Autschbach, F., Schurmann, G., Nishimoto, N., Yoshizaki, K., Ito, H., Kishimoto, T., Galle, P. R., Rose-John, S., and Neurath, M. F. (2000) Blockade of interleukin 6 trans-signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in Crohn’s disease and experimental colitis in vivo, Nature Med., 6, 583–588.

    Google Scholar 

  101. Ramiro, S., Gaujoux-Viala, C., Nam, J. L., Smolen, J. S., Buch, M., Gossec, L., Van Der Heijde, D., Winthrop, K., and Landewe, R. (2014) Safety of synthetic and biological DMARDs: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis, Ann. Rheum. Dis., 73, 529–535.

    CAS  PubMed  Google Scholar 

  102. Rubbert-Roth, A. (2012) Assessing the safety of biologic agents in patients with rheumatoid arthritis, Rheumatology, 51, 38–47.

    Google Scholar 

  103. Kaltsonoudis, E., Voulgari, P. V., Konitsiois, S., and Drosos, A. A. (2014) Demyelination and other neurological adverse events after anti-TNF therapy, Autoimmun. Rev., 13, 54–58.

    CAS  PubMed  Google Scholar 

  104. Prinz, J. C. (2011) Autoimmune-like syndromes during TNF blockade: does infection have a role? Nat. Rev. Rheumatol., 7, 429–434.

    CAS  PubMed  Google Scholar 

  105. Winsauer, C., Kruglov, A. A., Chashchina, A. A., Drutskaya, M. S., and Nedospasov, S. A. (2014) Cellular sources of pathogenic and protective TNF and experimental strategies on utilization of TNF humanized mice, Cytokine Growth Factor Rev., 25, 115–123.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Molecular Biology and Regional Ecology, Lobachevsky State University of Nizhni Novgorod, pr. Gagarina 23, 603950, Nizhni Novgorod, Russia

    I. V. Astrakhantseva, A. A. Kruglov & S. A. Nedospasov

  2. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, ul. Vavilova 32, 119991, Moscow, Russia

    G. A. Efimov, M. S. Drutskaya & S. A. Nedospasov

  3. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991, Moscow, Russia

    A. A. Kruglov & S. A. Nedospasov

  4. German Rheumatism Research Center, Leibnitz Institute, Chariteplatz 1, Berlin, 10117, Germany

    A. A. Kruglov & S. A. Nedospasov

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  1. I. V. Astrakhantseva
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  2. G. A. Efimov
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  3. M. S. Drutskaya
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  4. A. A. Kruglov
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  5. S. A. Nedospasov
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Correspondence to I. V. Astrakhantseva or S. A. Nedospasov.

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Original Russian Text © I. V. Astrakhantseva, G. A. Efimov, M. S. Drutskaya, A. A. Kruglov, S. A. Nedospasov, 2014, published in Biokhimiya, 2014, Vol. 79, No. 12, pp. 1605–1616.

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Astrakhantseva, I.V., Efimov, G.A., Drutskaya, M.S. et al. Modern anti-cytokine therapy of autoimmune diseases. Biochemistry Moscow 79, 1308–1321 (2014). https://doi.org/10.1134/S0006297914120049

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