Molecular targets in immune-mediated diseases: Focus on rheumatoid arthritis

Expert Opinion on Therapeutic Targets

Volumn 8, Issue 5, 2004, Pages 375-390

  Cook, Andrew D ^a   Visvanathan, Kumar ^a,b  

^a UNIVERSITY OF MELBOURNE   (Australia)

^b MURDOCH CHILDREN'S RESEARCH INSTITUTE   (Australia)

Author keywords

Biologics; Cytokines; Genomics; IL 1; Innate; Microarray; Proteomics; Rheumatoid arthritis (RA); TNF; Toll like receptor (TLR)

Indexed keywords

ACETYLSALICYLIC ACID; ADALIMUMAB; ALEMTUZUMAB; B7 ANTIGEN; C REACTIVE PROTEIN; CD20 ANTIBODY; CD28 ANTIGEN; CD52 ANTIGEN; CD86 ANTIGEN; CYCLOOXYGENASE 2 INHIBITOR; CYCLOSPORIN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; ECULIZUMAB; ETANERCEPT; HYBRID PROTEIN; INFLIXIMAB; INTERLEUKIN 12 ANTIBODY; INTERLEUKIN 2 RECEPTOR ANTIBODY; INTERLEUKIN 4; INTERLEUKIN 6 RECEPTOR BLOCKING AGENT; LEFLUNOMIDE; METHOTREXATE; MONOCLONAL ANTIBODY; NONSTEROID ANTIINFLAMMATORY AGENT; PLACEBO; RECOMBINANT INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; RECOMBINANT INTERLEUKIN 10; RETROVIRUS VECTOR; RITUXIMAB; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANTIGEN BINDING; CLINICAL TRIAL; DISEASE ACTIVITY; DRUG RESEARCH; DRUG TARGETING; ERYTHROCYTE SEDIMENTATION RATE; GENOMICS; HUMAN; IMMUNE DEFICIENCY; IMMUNE RESPONSE; IMMUNOLOGICAL MEMORY; IMMUNOSTIMULATION; INHIBITION KINETICS; LYMPHOCYTE ACTIVATION; META ANALYSIS; MOUSE; NONHUMAN; PAIN ASSESSMENT; PROTEOMICS; REVIEW; RHEUMATOID ARTHRITIS; SYSTEMATIC REVIEW; TREATMENT OUTCOME;

ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ANTIBODIES, MONOCLONAL; ARTHRITIS, RHEUMATOID; AUTOIMMUNE DISEASES; BIOLOGICAL RESPONSE MODIFIERS; CELL ADHESION MOLECULES; CYTOKINES; DISEASE MODELS, ANIMAL; DRUG DESIGN; GENE EXPRESSION REGULATION; GENE THERAPY; HUMANS; IMMUNITY, CELLULAR; IMMUNOCONJUGATES; IMMUNOLOGIC FACTORS; IMMUNOLOGIC MEMORY; IMMUNOSUPPRESSIVE AGENTS; IMMUNOTHERAPY; LYMPHOCYTE SUBSETS; MEMBRANE GLYCOPROTEINS; MICE; PROTEASE INHIBITORS; RECEPTORS, CELL SURFACE; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTORS;

EID: 5444251126     PISSN: 14728222     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728222.8.5.375     Document Type: Review

References (160)

1. FELDMANN M, MAINI RN: Anti-TNF α therapy of rheumatoid arthritis: what have we learned? Annu. Rev. Immunol (2001) 19:163-196.
2. LEE DM, WEINBLATT ME: Rheumatoid arthritis. Lancet (2001) 358(9285):903-911.
3. VAN DEN BERG WB: Uncoupling of inflammatory and destructive mechanisms in arthritis. Semin. Arthritis Rheum. (2001) 30(5 Suppl. 2):7-16.
4. DAOUD KF, JACKSON CG, WILLIAMS HJ: Basic therapy for rheumatoid arthritis: nonsteroidal anti-inflammatory drugs. Compr. Ther. (1999) 25(8-10):427-433.
5. TEN WOLDE S, HERMANS J, BREEDVELD FC, DIJKMANS BA: Effect of resumption of second line drugs in patients with rheumatoid arthritis that flared up after treatment discontinuation. Ann. Rheum. Dis. (1997) 56(4):235-239.
6. PALLADINO MA, BAHJAT FR, THEODORAKIS EA, MOLDAWER LL: Anti-TNF-α therapies: the next generation. Nat. Rev. Drug Discov. (2003) 2(9):736-746.
7. FELSON DT, ANDERSON JJ, BOERS M et al.: American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. (1995) 38(6 ):727-735.
8. ELLIOTT MJ, MAINI RN, FELDMANN M et al.: Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor α (cA2) versus placebo in rheumatoid arthritis. Lancet (1994) 344(8930):1105-1110.
9. MAINI RN, BREEDVELD FC, KALDEN JR et al.: Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor α monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum. (1998) 41(9):1552-1563.
10. MORELAND LW, BAUMGARTNER SW, SCHIFF MH et al.: Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N. Engl. J. Med. (1997) 337(3):141-147.
11. WEINBLATT ME, KREMER JM, BANKHURST AD et al.: A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N. Engl. J. Med. (1999) 340(4):253-259.
12. WEINBLATT ME, KEYSTONE EC, FURST DE et al.: Adalimumab, a fully human anti-tumor necrosis factor α monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum. (2003) 48(1):35-45.
13. LIPSKY PE, VAN DER HEIJDE DM, ST CLAIR EW et al.: Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N. Engl. J. Med. (2000) 343(22):1594-1602.
14. BATHON JM, MARTIN RW, FLEISCHMANN RM et al.: A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N. Engl. J. Med. (2000) 343(22):1586-1593.
15. PRESENT DH, RUTGEERTS P, TARGAN S et al.: Infliximab for the treatment of fistulas in patients with Crohn's disease. N. Engl. J. Med. (1999) 340(18):1398-1405.
16. CHAUDHARI U, ROMANO P, MULCAHY LD et al.: Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomised trial. Lancet (2001) 357(9271):1842-1847.
17. SIEPER J, BRAUN J: New treatment options in ankylosing spondylitis: a role for anti-TNFα therapy. Ann. Rheum. Dis. (2001) 60(Suppl. 3):iii58-61.
18. MEASE PJ: Cytokine blockers in psoriatic arthritis. Ann. Rheum. Dis. (2001) 60(Suppl. 3):iii37-40.
19. LOVELL DJ, GIANNINI EH, REIFF A et al.: Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. N. Engl. J. Med. (2000) 342(11):763-769.
20. LOVELL DJ, GIANNINI EH, REIFF A et al.: Long-term efficacy and safety of etanercept in children with polyarticular-course juvenile rheumatoid arthritis: interim results from an ongoing multicenter, open-label, extended-treatment trial. Arthritis Rheum. (2003) 48(1):218-226.
21. SKURKOVICH S, BOIKO A, BELIAEVA I et al.: Randomized study of antibodies to IFN-γ and TNF-α in secondary progressive multiple sclerosis. Mult. Scler. (2001) 7(5):277-284.
22. FIRESTEIN GS: Evolving concepts of rheumatoid arthritis. Nature (2003) 423(6937):356-361.
23. BRESNIHAN B, ALVARO-GRACIA JM, COBBY M et al.: Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Arthritis Rheum. (1998) 41(12):2196-2204.
24. JIANG Y, GENANT HK, WATT I et al.: A multicenter, double-blind, dose-ranging, randomized, placebo-controlled study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis: radiologic progression and correlation of Genant and Larsen scores. Arthritis Rheum. (2000) 43(5):1001-1009.
25. COHEN S, HURD E, CUSH J et al.: Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: results of a twenty-four-week, multicenter, randomized, double-blind, placeboHcontrolled trial. Arthritis Rheum. (2002) 46(3):614-624.
26. BUCH MH, BINGHAM SJ, SETO Y et al.: Lack of response to anakinra in rheumatoid arthritis following failure of tumor necrosis factor α blockade. Arthritis Rheum. (2004) 50(3):725-728.
27. ZWERINA J, HAYER S, TOHIDAST-AKRAD M et al.: Single and combined inhibition of tumor necrosis factor, interleukin-1, and RANKL pathways in tumor necrosis factor-induced arthritis: effects on synovial inflammation, bone erosion, and cartilage destruction. Arthritis Rheum. (2004) 50(1):277-290.
28. WALSH DA, HAYWOOD L: Angiogenesis: a therapeutic target in arthritis. Curr. Opin. Investig. Drugs (2001) 2(8):1054-1063.
29. ABRAMSON SB, AMIN A: Blocking the effects of IL-1 in rheumatoid arthritis protects bone and cartilage. Rheumatology (2002) 41(9):972-980.
30. CHOY EH, ISENBERG DA, GARROOD T et al.: Therapeutic benefit of blocking interleukin-6 activity with an anti-interleukin-6 receptor monoclonal antibody in rheumatoid arthritis: a randomized, double-blind, placebo-controlled, dose-escalation trial. Arthritis Rheum. (2002) 46(12):3143-3150.
31. VANDENBROECK K, ALLOZA I, GADINA M, MATTHYS P: Inhibiting cytokines of the interleukin-12 family: recent advances and novel challenges. J. Pharm. Pharmacol. (2004) 56(2):145-160.
32. KIM TS, KANG BY, LEE MH, CHOE YK, HWANG SY: Inhibition of interleukin-12 production by auranofin, an anti-rheumatic gold compound, deviates CD4(+) T cells from the Th1 to the Th2 pathway. Br. J. Pharmacol. (2001) 134(3):571-578.
33. KANG BY, CHUNG SW, IM SY, CHOE YK, KIM TS: Sulfasalazine prevents T-helper 1 immune response by suppressing interleukin-12 production in macrophages. Immunology (1999) 98(1):98-103.
34. KANG BY, CHUNG SW, KIM SH et al.: Retinoid-mediated inhibition of interleukin-12 production in mouse macrophages suppresses Th1 cytokine profile in CD4(+) T cells. Br. J. Pharmacol. (2000) 130(3):581-586.
35. BUTLER DM, MALFAIT AM, MAINI RN, BRENNAN FM, FELDMANN M: Anti-IL-12 and anti-TNF antibodies synergistically suppress the progression of routine collagen-induced arthritis. Eur. J. Immunol. (1999) 29(7):2205-2212.
36. MURPHY CA, LANGRISH CL, CHEN Y et al.: Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J. Exp. Med. (2003) 198(12):1951-1957.
37. STROM TB, KELLEY VR, MURPHY JR, NICHOLS J, WOODWORTH TG: Interleukin-2 receptor-directed therapies: antibody- or cytokine-based targeting molecules. Annu. Rev. Med. (1993) 44:343-353.
38. MORELAND LW, SEWELL KL, TRENTHAM DE et al.: Interleukin-2 diphtheria fusion protein (DAB486IL-2) in refractory rheumatoid arthritis. A double-blind, placebo-controlled trial with open-label extension. Arthritis Rheum. (1995) 38(9):1177-1186.
39. GOTTLIEB SL, GILLEAUDEAU P, JOHNSON R et al.: Response of psoriasis to a lymphocyte-selective toxin (DAB389IL-2) suggests a primary immune, but not keratinocyte, pathogenic basis. Nat. Med. (1995) 1(5):442-447.
40. RUCHATZ H, LEUNG BP, WEI XQ, MCINNES IB, LIEW FY: Soluble IL-15 receptor α-chain administration prevents murine collagen-induced arthritis: a role for IL-15 in development of antigen-induced immunopathology. J. Immunol. (1998) 160(11):5654-5660.
41. LIEW FY, MCINNES IB: Role of interleukin 15 and interleukin 18 in inflammatory response. Ann. Rheum. Dis. (2002) 61(Suppl. 2):ii100-102.
42. STAMP LK, JAMES MJ, CLELAND LG: Interleukin-17: the missing link between T-cell accumulation and effector cell actions in rheumatoid arthritis? Immunol. Cell Biol. (2004) 82(1):1-9.
43. NAKAE S, SAIJO S, HORAI R et al.: IL-17 production from activated T cells is required for the spontaneous development of destructive arthritis in mice deficient in IL-1 receptor antagonist. Proc. Natl. Acad. Sci. USA (2003) 100(10):5986-5990.
44. LUBBERTS E, KOENDERS MI, OPPERS-WALGREEN B et al.: Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion. Arthritis Rheum. (2004) 50(2):650-659.
45. 2 in interleukin 17 stimulated human monocytes/macrophages. J. Rheumatol. (2001) 28(4):712-718.
46. CHABAUD M, MIOSSEC P: The combination of tumor necrosis factor α blockade with interleukin-1 and interleukin-17 blockade is more effective for controlling synovial inflammation and bone resorption in an ex vivo model. Arthritis Rheum. (2001) 44(6):1293-1303.
47. GRACIE JA, FORSEY RJ, CHAN WL et al.: A proinflammatory role for IL-18 in rheumatoid arthritis. J. Clin. Invest. (1999) 104(10):1393-1401.
48. SUGAYA M, NAKAMURA K, TAMAKI K: Interleukins 18 and 12 synergistically upregulate interferon-γ production by murine dendritic epidermal T cells. J. Invest. Dermatol. (1999) 113(3):350-354.
49. WEI XQ, LEUNG BP, ARTHUR HM, MCINNES IB, LIEW FY: Reduced incidence and severity of collagen-induced arthritis in mice lacking IL-18. J. Immunol. (2001) 166(1):517-521.
50. PLATER-ZYBERK C, JOOSTEN LA, HELSEN MM et al.: Therapeutic effect of neutralizing endogenous IL-18 activity in the collagen-induced model of arthritis. J. Clin. Invest. (2001) 108(12):1825-1832.
51. SMEETS RL, VAN DE LOO FA, ARNTZ OJ et al.: Adenoviral delivery of IL-18 binding protein C ameliorates collagen-induced arthritis in mice. Gene Ther. (2003) 10(12):1004-1011.
52. LOCHNER M, FORSTER I: Anti-interleukin-18 therapy in murine models of inflammatory bowel disease. Pathobiology (2002) 70(3):164-169.
53. KANAI T, URAUSHIHARA K, TOTSUKA T et al.: Macrophage-derived IL-18 targeting for the treatment of Crohn's disease. Curr. Drug Targets Inflamm. Allergy (2003) 2(2):131-136.
54. HAMILTON JA: GM-CSF in inflammation and autoimmunity. Trends Immunol. (2002) 23(8):403-408.
55. CAMPBELL IK, RICH MJ, BISCHOF RJ et al.: Protection from collagen-induced arthritis in granulocyte-macrophage colony-stimulating factor-deficient mice. J. Immunol. (1998) 161(7):3639-3644.
56. YANG YH, HAMILTON JA: Dependence of interleukin-1-induced arthritis on granulocyte-macrophage colony-stimulating factor. Arthritis Rheum. (2001) 44(1):111-119.
57. COOK AD, BRAINE EL, CAMPBELL IK, RICH MJ, HAMILTON JA: Blockade of collagen-induced arthritis post-onset by antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF): requirement for GM-CSF in the effector phase of disease. Arthritis Res. (2001) 3(5):293-298.
58. MCQUALTER JL, DARWICHE R, EWING C et al.: Granulocyte macrophage colony-stimulating factor: a new putative therapeutic target in multiple sclerosis. J. Exp. Med. (2001) 194(7):873-882.
59. KITCHING AR, RU HUANG X, TURNER AL et al.: The requirement for granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in leukocyte-mediated immune glomerular injury. J. Am. Soc. Nephrol. (2002) 13(2):350-358.
60. BOZINOVSKI S, JONES JE, VLAHOS R, HAMILTON JA, ANDERSON GP: Granulocyte/macrophage colony-stimulating factor (GM-CSF) regulates lung innate immunity to lipopolysaccharide through Akt/Erk activation of NFκB and AP-1 in vivo. J. Biol. Chem. (2002) 277(45):42808-42814.
61. BOZINOVSKI S, JONES J, BEAVITT SJ et al.: Innate immune responses to LPS in mouse lung are suppressed and reversed by neutralization of GM-CSF via repression of TLR-4. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) 286(4):L877-L885.
62. YANG N, NIKOLIC-PATERSON DJ, NG YY et al.: Reversal of established rat crescentic glomerulonephritis by blockade of macrophage migration inhibitory factor (MIF): potential role of MIF in regulating glucocorticoid production. Mol. Med. (1998) 4(6):413-424.
63. LEECH M, METZ C, SANTOS L et al.: Involvement of macrophage migration inhibitory factor in the evolution of rat adjuvant arthritis. Arthritis Rheum. (1998) 41(5):910-917.
64. DE JONG YP, ABADIA-MOLINA AC, SATOSKAR AR et al.: Development of chronic colitis is dependent on the cytokine MIF. Nat. Immun. (2001) 2(11):1061-1066.
65. TARNER IH, NAKAJIMA A, SEROOGY CM et al.: Retroviral gene therapy of collagen-induced arthritis by local delivery of IL-4. Clin. Immunol. (2002) 105(3):304-314.
66. JOOSTEN LA, LUBBERTS E, DUREZ P et al.: Role of interleukin-4 and interleukin-10 in murine collagen-induced arthritis. Protective effect of interleukin-4 and interleukin-10 treatment on cartilage destruction. Arthritis Rheum. (1997) 40(2):249-260.
67. MARTIN R: Interleukin 4 treatment of psoriasis: are pleiotropic cytokines suitable therapies for autoimmune diseases? Trends Pharmacol. Sci. (2003) 24(12):613-616.
68. KEYSTONE E, WHERRY J, GRINT P: IL-10 as a therapeutic strategy in the treatment of rheumatoid arthritis. Rheum. Dis. Clin. North Am. (1998) 24(3):629-639.
69. LI MC, HE SH: IL-10 and its related cytokines for treatment of inflammatory bowel disease. World J. Gastroenterol. (2004) 10(5):620-625.
70. BESSIS N, BOISSIER MC, FERRARA P et al.: Attenuation of collagen-induced arthritis in mice by treatment with vector cells engineered to secrete interleukin-13. Eur. J. Immunol. (1996) 26(10):2399-2403.
71. WOODS JM, AMIN MA, KATSCHKE KJ Jr et al.: Interleukin-13 gene therapy reduces inflammation, vascularization, and bony destruction in rat adjuvant-induced arthritis. Hum. Gene Ther. (2002) 13(3):381-393.
72. 2 by IL-13 gene therapy in rheumatoid arthritis synovium. J. Immunol. (2000) 165(5):2755-2763.
73. MAEDA T, SAIKAWA I, HOTOKEBUCHI T et al.: Exacerbation of established collagen-induced arthritis in mice treated with an anti-T cell receptor antibody. Arthritis Rheum. (1994) 37(3):406-413.
74. MORELAND LW, HAVERTY TP, WACHOLTZ MC et al.: Nondepleting humanized anti-CD4 monoclonal antibody in patients with refractory rheumatoid arthritis. J. Rheumatol. (1998) 25(2):221-228.
75. SCHULZE-KOOPS H, DAVIS LS, HAVERTY TP, WACHOLTZ MC, LIPSKY PE: Reduction of Th1 cell activity in the peripheral circulation of patients with rheumatoid arthritis after treatment with a non-depleting humanized monoclonal antibody to CD4. J Rheumatol. (1998) 25(11):2065-2076.
76. UTSET TO, AUGER JA, PEACE D et al.: Modified anti-CD3 therapy in psoriatic arthritis: a Phase I/II clinical trial. J. Rheumatol. (2002) 29(9):1907-1913.
77. MATTESON EL, YOCUM DE, ST CLAIR EW et al.: Treatment of active refractory rheumatoid arthritis with humanized monoclonal antibody CAMPATH-1H administered by daily subcutaneous injection. Arthritis Rheum. (1995) 38(9):1187-1193.
78. BRETT SJ, BAXTER G, COOPER H et al.: Emergence of CD52-, glycosylphosphatidylinositol-anchor-deficient lymphocytes in rheumatoid arthritis patients following CAMPATH-1 H treatment. Int. Immunol. (1996) 8(3):325-334.
79. BRETT S, BAXTER G, COOPER H et al.: Repopulation of blood lymphocyte sub-populations in rheumatoid arthritis patients treated with the depleting humanized monoclonal antibody, CAMPATH-1H. Immunology (1996) 88(1):13-19.
80. MALEK TR: The main function of IL-2 is to promote the development of T regulatory cells. J. Leukoc. Biol. (2003) 74(6):961-965.
81. BANERJEE S, WEI BY, HILLMAN K, LUTHRA HS, DAVID CS: Immunosuppression of collagen-induced arthritis in mice with an anti-IL-2 receptor antibody. J. Immunol. (1988) 141(4):1150-1154.
82. MORGAN ME, SUTMULLER RP, WITTEVEEN HJ et al.: CD25+ cell depletion hastens the onset of severe disease in collagen-induced arthritis. Arthritis Rheum. (2003) 48(5):1452-1460.
83. SLAVIK JM, HUTCHCROFT JE, BIERER BE: CD28/CTLA-4 and CD80/CD86 families: signaling and function. Immunol. Res. (1999) 19(1):1-24.
84. MORELAND LW, ALTEN R, VAN DEN BOSCH F et al.: Costimulatory blockade in patients with rheumatoid arthritis: a pilot, dose-finding, double-blind, placebo-controlled clinical trial evaluating CTLA-4Ig and LEA29Y eighty-five days after the first infusion. Arthritis Rheum. (2002) 46(6):1470-1479.
85. KREMER JM, WESTHOVENS R, LEON M et al.: Treatment of rheumatoid arthritis by selective inhibition of T -cell activation with fusion protein CTLA4Ig. N. Engl. J. Med. (2003) 349(20):1907-1915.
86. SCHONBECK U, LIBBY P: The CD40/CD154 receptor/ligand dyad. Cell. Mol. Life Sci. (2001) 58(1):4-43.
87. DAIKH DI, WOFSY D: Treatment of autoimmunity by inhibition of T cell costimulation. Adv. Exp. Med. Biol. (2001) 490:113-117.
88. YOSHINAGA SK, WHORISKEY JS, KHARE SD et al.: T-cell co-stimulation through B7RP-1 and ICOS. Nature (1999) 402(6763):827-832.
89. NURIEVA RI, TREUTING P, DUONG J, FLAVELL RA, DONG C: Inducible costimulator is essential for collagen-induced arthritis. J. Clin. Invest. (2003) 111(5):701-706.
90. IWAI H, KOZONO Y, HIROSE S et al.: Amelioration of collagen-induced arthritis by blockade of inducible costimulator-B7 homologous protein costimulation. J. Immunol. (2002) 169(8):4332-4339.
91. ROTTMAN JB, SMITH T, TONRA JR et al.: The costimulatory molecule ICOS plays an important role in the immunopathogenesis of EAE. Nat. Immunol. (2001) 2(7):605-611.
92. GONZALO JA, TIAN J, DELANEY T et al.: ICOS is critical for T helper cell-mediated lung mucosal inflammatory responses. Nat. Immunol. (2001) 2(7):597-604.
93. YAMAZAKI T, AKIBA H, IWAI H et al.: Expression of programmed death 1 ligands by murine T cells and APC. J. Immunol. (2002) 169(10):5538-5545.
94. NISHIMURA H, NOSE M, HIAI H, MINATO N, HONJO T: Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity (1999) 11(2):141-151.
95. OKAZAKI T, IWAI Y, HONJO T: New regulatory co-receptors: inducible co-stimulator and PD-1. Curr. Opin. Immunol. (2002) 14(6):779-782.
96. BROWN JA, DORFMAN DM, MA FR et al.: Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J. Immunol. (2003) 170(3):1257-1266.
97. KANAI T, TOTSUKA T, URAUSHIHARA K et al.: Blockade of B7-H1 suppresses the development of chronic intestinal inflammation. J. Immunol. (2003) 171(8):4156-4163.
98. DE VITA S, ZAJA F, SACCO S et al.: Efficacy of selective B cell blockade in the treatment of rheumatoid arthritis: evidence for a pathogenetic role of B cells. Arthritis Rheum. (2002) 46(8):2029-2033.
99. LEANDRO MJ, EDWARDS JC, CAMBRIDGE G: Clinical outcome in 22 patients with rheumatoid arthritis treated with B lymphocyte depletion. Ann. Rheum. Dis. (2002) 61(10):883-888.
100. VEGA MI, HUERTA-YEPAZ S, GARBAN H et al.: Rituximab inhibits p38-MAPK activity in 2F7 B NHL and decreases IL-10 transcription: pivotal role of p38-MAPK in drug resistance. Oncogene (2004) 23(20):3530-3540.
101. LOONEY RJ, ANOLIK J, SANZ I: B cells as therapeutic targets for rheumatic diseases. Curr. Opin. Rheumatol. (2004) 16(3):180-185.
102. KAVANAUGH AF, DAVIS LS, NICHOLS LA et al.: Treatment of refractory rheumatoid arthritis with a monoclonal antibody to intercellular adhesion molecule 1. Arthritis Rheum. (1994) 37(7):992-999.
103. KAVANAUGH AF, DAVIS LS, JAIN RI et al.: A Phase I/II open label study of the safety and efficacy of an anti-ICAM-1 (intercellular adhesion molecule-1; CD54) monoclonal antibody in early rheumatoid arthritis. J. Rheumatol. (1996) 23(8):1338-1344.
104. KAVANAUGH AF, SCHULZE-KOOPS H, DAVIS LS, LIPSKY PE: Repeat treatment of rheumatoid arthritis patients with a murine anti-intercellular adhesion molecule 1 monoclonal antibody. Arthritis Rheum. (1997) 40(5):849-853.
105. ELLIS CN, KRUEGER GG: Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. N. Engl. J. Med. (2001) 345(4):248-255.
106. KRUEGER GG: Selective targeting of T cell subsets: focus on alefacept - a remittive therapy for psoriasis. Expert Opin. Biol. Ther. (2002) 2(4):431-441.
107. DA SILVA AJ, BRICKELMAIER M, MAJEAU GR et al.: Alefacept, an immunomodulatory recombinant LFA-3/IgG1 fusion protein, induces CD16 signaling and CD2/CD16-dependent apoptosis of CD2(+) cells. J. Immunol. (2002) 168(9):4462-4471.
108. PAPP K, BISSONNETTE R, KRUEGER JG et al.: The treatment of moderate to severe psoriasis with a new anti-CD11 a monoclonal antibody. J. Am. Acad. Dermatol. (2001) 45(5):665-674.
109. TUTRONE WD, KAGEN MH, BARBAGALLO J, WEINBERG JM: Biologic therapy for psoriasis: a brief history, II. Cutis (2001) 68(6):367-372.
110. RAYCHAUDHURI A, CHOU M, WEETALL M, JENG AY: Blockade of integrin VLA-4 prevents inflammation and matrix metalloproteinase expression in a murine model of accelerated collagen-induced arthritis. Inflammation (2003) 27(2):107-113.
111. GORDON FH, HAMILTON MI, DONOGHUE S et al.: A pilot study of treatment of active ulcerative colitis with natalizumab, a humanized monoclonal antibody to α-4 integrin. Aliment. Pharmacol. Ther. (2002) 16(4):699-705.
112. GHOSH S, GOLDIN E, GORDON FH et al.: Natalizumab for active Crohn's disease. N. Engl. J. Med. (2003) 348(1):24-32.
113. GORDON FH, LAI CW, HAMILTON MI et al.: A randomized placebo-controlled trial of a humanized monoclonal antibody to α4 integrin in active Crohn's disease. Gastroenterology (2001) 121(2):268-274.
114. TUBRIDY N, BEHAN PO, CAPILDEO R et al.: The effect of anti-α4 integrin antibody on brain lesion activity in MS. The UK Antegren Study Group. Neurology (1999) 53(3):466-472.
115. DALTON CM, MISZKIEL KA, BARKER GJ et al.: Effect of natalizumab on conversion of gadolinium enhancing lesions to T1 hypointense lesions in relapsing multiple sclerosis. J. Neurol. (2004) 251(4):407-413.
116. ALAHARI SK, REDDIG PJ, JULIANO RL: Biological aspects of signal transduction by cell adhesion receptors. Int. Rev. Cytol. (2002) 220:145-184.
117. KONTTINEN YT, AINOLA M, VALLEALA H et al.: Analysis of 16 different matrix metalloproteinases (MMP-1 to MMP-20) in the synovial membrane: different profiles in trauma and rheumatoid arthritis. Ann. Rheum. Dis. (1999) 58(11):691-697.
118. SADOWSKI T, STEINMEYER J: Effects of tetracyclines on the production of matrix metalloproteinases and plasminogen activators as well as of their natural inhibitors, tissue inhibitor of metalloproteinases-1 and plasminogen activator inhibitor-1. Inflamm. Res. (2001) 50(3):175-182.
119. DEAGE V, BURGER D, DAYER JM: Exposure of T lymphocytes to leflunomide but not to dexamethasone favors the production by monocytic cells of interleukin-1 receptor antagonist and the tissue-inhibitor of metalloproteinases-1 over that of interleukin-1 beta and metalloproteinases. Eur. Cytokine Netw. (1998) 9(4):663-668.
120. HAMADA T, ARIMA N, SHINDO M, SUGAMA K, SASAGURI Y: Suppression of adjuvant arthritis of rats by a novel matrix metalloproteinase-inhibitor. Br. J. Pharmacol. (2000) 131(8):1513-1520.
121. CELIKER MY, RAMAMURTHY N, XU JW et al.: Inhibition of adjuvant-induced arthritis by systemic tissue inhibitor of metalloproteinases 4 gene delivery. Arthritis Rheum. (2002) 46(12):3361-3368.
122. CLOSE DR: Matrix metalloproteinase inhibitors in rheumatic diseases. Ann. Rheum. Dis. (2001) 60(Suppl. 3):iii62-67.
123. KEYSTONE E: Treatments no longer in development for rheumatoid arthritis. Ann. Rheum. Dis. (2002) 61(Suppl. 2):ii43-45.
124. NEUMANN E, BARNUM SR, TARNER IH et al.: Local production of complement proteins in rheumatoid arthritis synovium. Arthritis Rheum. (2002) 46(4):934-945.
125. WANG Y, ROLLINS SA, MADRI JA, MATIS LA: Anti-C5 monoclonal antibody therapy prevents collagen-induced arthritis and ameliorates established disease. Proc. Natl. Acad. Sci. USA (1995) 92(19):8955-8959.
126. KAPLAN M: Eculizumab (Alexion). Curr. Opin. Investig. Drugs (2002) 3(7):1017-1023.
127. SCHNARE M, BARTON GM, HOLT AC et al.: Toll-like receptors control activation of adaptive immune responses. Nat. Immun. (2001) 2(10):947-950.
128. PASARE C, MEDZHITOV R: Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science (2003) 299(5609):1033-1036.
129. JOOSTEN LA, KOENDERS MI, SMEETS RL et al.: Toll-like receptor 2 pathway drives streptococcal cell wall-induced joint inflammation: critical role of myeloid differentiation factor 88. J. Immunol. (2003) 171(11):6145-6153.
130. DENG GM, NILSSON IM, VERDRENGH M, COLLINS LV, TARKOWSKI A: Intra-articularly localized bacterial DNA containing CpG motifs induces arthritis. Nat. Med. (1999) 5(6):702-705.
131. DENG GM, TARKOWSKI A: The features of arthritis induced by CpG motifs in bacterial DNA. Arthritis Rheum. (2000) 43(2):356-364.
132. YOSHINO S, SASATOMI E, OHSAWA M: Bacterial lipopolysaccharide acts as an adjuvant to induce autoimmune arthritis in mice. Immunology (2000) 99(4):607-614.
133. CHOE JY, CRAIN B, WU SR, CORR M: Interleukin 1 receptor dependence of serum transferred arthritis can be circumvented by toll-like receptor 4 signaling. J. Exp. Med. (2003) 197(4):537-542.
134. BEG AA: Endogenous ligands of toll-like receptors: implications for regulating inflammatory and immune responses. Trends Immunol. (2002) 23(11):509-512.
135. LEADBETTER EA, RIFKIN IR, HOHLBAUM AM et al.: Chromatin-IgG complexes activate B cells by dual engagement of IgM and toll-like receptors. Nature (2002) 416(6881):603-607.
136. SCHETT G, TOHIDAST-AKRAD M, SMOLEN JS et al.: Activation, differential localization, and regulation of the stress-activated protein kinases, extracellular signal-regulated kinase, c-JUN N-terminal kinase, and p38-mitogen-activated protein kinase, in synovial tissue and cells in rheumatoid arthritis. Arthritis Rheum. (2000) 43(11):2501-2512.
137. ADAMS JL, BADGER AM, KUMAR S, LEE JC: p38-MAP kinase: molecular target for the inhibition of pro-inflammatory cytokines. Prog. Med. Chem. (2001) 38:1-60.
138. BADGER AM, BRADBEER JN, VOTTA B et al.: Pharmacological profile of SB 203580, a selective inhibitor of cytokine suppressive binding protein/p38 kinase, in animal models of arthritis, bone resorption, endotoxin shock and immune function. J. Pharmacol. Exp. Ther. (1996) 279(3):1453-1461.
139. BADGER AM, GRISWOLD DE, KAPADIA R et al.: Disease-modifying activity of SB 242235, a selective inhibitor of p38-mitogen-activated protein kinase, in rat adjuvant-induced arthritis. Arthritis Rheum. (2000) 43(1):175-183.
140. COLLIS AJ, FOSTER ML, HALLEY F et al.: RPR203494 a pyrimidine analogue of the p38 inhibitor RPR200765A with an improved in vitro potency. Bioorg. Med. Chem. Lett. (2001) 11(5):693-696.
141. KUMAR S, BOEHM J, LEE JC: p38-MAP kinases: key signalling molecules as therapeutic targets for inflammatory diseases. Nat. Rev. Drug Discov. (2003) 2(9):717-726.
142. MINDEN A, KARIN M: Regulation and function of the JNK subgroup of MAP kinases. Biochim. Biophys. Acta (1997) 1333(2):F85-F104.
143. HAN Z, BOYLE DL, CHANG L et al.: c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. J. Clin. Invest. (2001) 108(1):73-81.
144. JIMI E, AOKI K, SAITO H et al.: Selective inhibition of NF-1κB blocks osteoclastogenesis and prevents inflammatory bone destruction in vivo. Nat. Med. (2004) 10(6):617-624.
145. CLOHISY JC, ROY BC, BIONDO C et al.: Direct inhibition of NF-κB blocks bone erosion associated with inflammatory arthritis. J. Immunol. (2003) 171(10):5547-5553.
146. KARIN M, YAMAMOTO Y, WANG QM: The IKK NF-κB system: a treasure trove for drug development. Nat. Rev. Drug Discov. (2004) 3(1):17-26.
147. HARRISON LC, HAFLER DA: Antigen-specific therapy for autoimmune disease. Curr. Opin. Immunol. (2000) 12(6):704-711.
148. KITANO H: Systems biology: a brief overview. Science (2002) 295(5560):1662-1664.
149. GRANT EP, PICKARD MD, BRISKIN MJ, GUTIERREZ-RAMOS JC: Gene expression profiles: creating new perspectives in arthritis research. Arthritis Rheum. (2002) 46(4):874-884.
150. VAN DER POUW KRAAN TC, VAN GAALEN FA, HUIZINGA TW et al.: Discovery of distinctive gene expression profiles in rheumatoid synovium using cDNA microarray technology: evidence for the existence of multiple pathways of tissue destruction and repair. Genes Immun. (2003) 4(3):187-196.
151. CROW MK, WOHLGEMUTH J: Microarray analysis of gene expression in lupus. Arthritis Res. Ther. (2003) 5(6):279-287.
152. WANDINGER KP, STURZEBECHER CS, BIELEKOVA B et al.: Complex immunomodulatory effects of interferon-β in multiple sclerosis include the upregulation of T helper 1-associated marker genes. Ann. Neurol. (2001) 50(3):349-357.
153. SAUTER G, SIMON R, HILLAN K: Tissue microarrays in drug discovery. Nat. Rev. Drug Discov. (2003) 2(12):962-972.
154. LORENZ P, RUSCHPLER P, KOCZAN D, STIEHL P, THIESEN HJ: From transcriptome to proteome: differentially expressed proteins identified in synovial tissue of patients suffering from rheumatoid arthritis and osteoarthritis by an initial screen with a panel of 791 antibodies. Proteomics (2003) 3(6):991-1002.
155. AEBERSOLD R, MANN M: Mass spectrometry-based proteomics. Nature (2003) 422(6928):198-207.
156. SINZ A, BANTSCHEFF M, MIKKAT S et al.: Mass spectrometric proteome analyses of synovial fluids and plasmas from patients suffering from rheumatoid arthritis and comparison to reactive arthritis or osteoarthritis. Electrophoresis (2002) 23(19):3445-3456.
157. TEMPLIN MF, STOLL D, SCHRENK M et al.: Protein microarray technology. Drug Discov. Today (2002) 7(15):815-822.
158. LUEKING A, HORN M, EICKHOFF H et al.: Protein microarrays for gene expression and antibody screening. Anal. Biochem. (1999) 270(1):103-111.
159. WALTER G, BUSSOW K, CAHILL D, LUEKING A, LEHRACH H: Protein arrays for gene expression and molecular interaction screening. Curr. Opin. Microbiol. (2000) 3(3):298-302.
160. PAULUS HE, EGGER MJ, WARD JR, WILLIAMS HJ: Analysis of improvement in individual rheumatoid arthritis patients treated with disease-modifying antirheumatic drugs, based on the findings in patients treated with placebo. The Cooperative Systematic Studies of Rheumatic Diseases Group. Arthritis Rheum. (1990) 33(4):477-484.