Targeting cytokines in autoimmunity: New approaches, new promise

Expert Opinion on Biological Therapy

Volumn 3, Issue 3, 2003, Pages 435-447

  Andreakos, Evangelos ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

Autoimmunity; Crohn's disease; Cytokines; MAPK; Monoclonal antibody; NF B; Psoriasis; Rheumatoid arthritis; Signalling; TNF

Indexed keywords

ADALIMUMAB; CERTOLIZUMAB PEGOL; CYCLOSPORIN A; CYTOKINE; DEXAMETHASONE; ETANERCEPT; GLUCOCORTICOID; GOLD; HYBRID PROTEIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INFLIXIMAB; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; INTERLEUKIN 10 ANTIBODY; INTERLEUKIN 10 RECEPTOR; INTERLEUKIN 10 RECEPTOR ANTIBODY; INTERLEUKIN 11; INTERLEUKIN 6 ANTIBODY; INTERLEUKIN 8; INTERLEUKIN 8 ANTIBODY; LEFLUNOMIDE; LENERCEPT; METHOTREXATE; NONSTEROID ANTIINFLAMMATORY AGENT; PENICILLAMINE; RECOMBINANT INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; SALAZOSULFAPYRIDINE; TACROLIMUS; TUMOR NECROSIS FACTOR ALPHA ANTIBODY; TUMOR NECROSIS FACTOR RECEPTOR; UNCLASSIFIED DRUG; UNINDEXED DRUG;

AUTOIMMUNE DISEASE; AUTOIMMUNITY; CLINICAL TRIAL; CROHN DISEASE; HUMAN; JUVENILE RHEUMATOID ARTHRITIS; PATHOPHYSIOLOGY; PSORIATIC ARTHRITIS; REVIEW; RHEUMATOID ARTHRITIS; SIGNAL TRANSDUCTION;

ANIMALS; AUTOIMMUNE DISEASES; CYTOKINES; DRUG DELIVERY SYSTEMS; HUMANS; SIGNAL TRANSDUCTION;

EID: 0038540674     PISSN: 14712598     EISSN: None     Source Type: Journal    
DOI: 10.1517/14712598.3.3.435     Document Type: Review

References (137)

1. FELDMANN M, BRENNAN FM, MAINI RN: Role of cytokines in rheumatoid arthritis. Annu. Rev. Immunol. (1996) 14:397-440.
2. FELDMANN M, MAINI RN: Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned? Annu. Rev. Immunol. (2001) 19:163-196. A detailed review of the and-TNF-α therapy in RA.
3. ANDREAKOS E, FOXWELL B, BRENNAN F et al.: Cytokines and anti-cytokine biologicals in autoimmunity: present and future. Cytokine Growth Factor Rev. (2002) 13(4-5):299-313. An overview of anticytokine therapy in autoimmunity.
4. BRENNAN FM, CHANTRY D, JACKSON A et al.: Inhibitory effect of TNF alpha antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet (1989) 2(8657):244-247. The initial discovery that TNF-α orchestrates the cytokine network in RA.
5. BUTLER DM, MAINI RN, FELDMANN M et al.: Modulation of proinflammatory cytokine release in rheumatoid synovial membrane cell cultures. Comparison of monoclonal anti TNF-alpha antibody with the interleukin-1 receptor antagonist. Eur. Cytokine Netw. (1995) 6(4):225-230.
6. HAWORTH C, BRENNAN FM, CHANTRY D et al.: Expression of granulocyte-macrophage colony-stimulating factor in rheumatoid arthritis: regulation by tumor necrosis factor-alpha. Eur. J. Immunol. (1991) 21(10):2575-2579.
7. FELDMANN M, BRENNAN FM, MAINI RN: Rheumatoid arthritis. Cell (1996) 85(3):307-310.
8. ALVARO-GRACIA JM, ZVAIFLER NJ, BROWN CB et al.: Cytokines in chronic inflammatory arthritis. VI. Analysis of the synovial cells involved in granulocyte-macrophage colony-stimulating factor production and gene expression in rheumatoid arthritis and its regulation by IL-1 and tumor necrosis factor-alpha. J. Immunol. (1991) 146(10):3365-3371.
9. THORBECKE GJ, SHAH R, LEU CH et al.: Involvement of endogenous tumor necrosis factor alpha and transforming growth factor beta during induction of collagen type II arthritis in mice. Proc. Natl. Acad. Sci. USA (1992) 89(16):7375-7379.
10. WILLIAMS RO, FELDMANN M, MAINI RN: Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. Proc. Natl. Acad. Sci. USA (1992) 89(20):9784-9788,
11. PIGUET PF, GRAU GE, VESIN C et al.: Evolution of collagen arthritis in mice is arrested by treatment with anti-tumour necrosis factor (TNF) antibody or a recombinant soluble TNF receptor. Immunology (1992) 77(4):510-514.
12. WOOLEY PH, DUTCHER J, WIDMER MB et al.: Influence of a recombinant human soluble tumor necrosis factor receptor FC fusion protein on type II collagen-induced arthritis in mice. J. Immunol. (1993) 151(11):6602-6607.
13. KNIGHT DM, TRINH H, LE J et al.: Construction and initial characterization of a mouse-human chimeric anti-TNF antibody. Mol. Immunol. (1993) 30(16):1443-1453.
14. ELLIOTT MJ, MAINI RN, FELDMANN M et al.: Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to rumor necrosis factor alpha. Arthritis Rheum. (1993) 36(12):1681-1690. The first results of anti-TNF-α therapy in RA.
15. MAINI RN, BREEDVELD FC, KALDEN JR et al.: Therapeutic efficacy of multiple intravenous infusions of antitumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum. (1998) 41(9):1552-1563.
16. MAINI R, ST CLAIR EW, BREEDVELD F et al.: Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet (1999) 354(9194):1932-1939.
17. 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.
18. 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.
19. 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.
20. 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.
21. KEMPENI J: Update on D2E7: a fully human anti-tumour necrosis factor alpha monoclonal antibody. Ann. Rheum. Dis. (2000) 59(Suppl. 1):i44-i45.
22. DEN BROEDER AA, JOOSTEN LA, SAXNE T et al.: Long term anti-tumour necrosis factor alpha monotherapy in rheumatoid arthritis: effect on radiological course and prognostic value of markers of cartilage turnover and endothelial activation. Ann. Rheum. Dis. (2002) 61(4):311-318.
23. HAZLEMAN B, SMITH M, MOSS K et al.: Efficacy of a novel PEGylated humanised anti-TNF fragment (CDP870) in patients with rheumatoid arthritis. Rheumatology (2000) 39(Suppl.):87.
24. DAVIS MW, FEIGE U, BENDELE AM et al.: Treatment of rheumatoid arthritis with PEGylated recombinant human soluble tumour necrosis factor receptor type I: a clinical update. Ann. Rheum. Dis. (2000) 59(Suppl. 1):i41-i43.
25. RUTGEERTS P, D'HAENS G, VAN DEVENTER SJ: Retreatment with anti-TNFa chimeric antibody (cA2) effectively maintains cA2-induced remission in Crohn's disease. Gastroenterology (1997) 112:a1078.
26. RUTGEERTS P, D'HAENS G, TARGAN S et al.: Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn's disease. Gastroenterology (1999) 117(4):761-769.
27. D'HAENS G, VAN DEVENTER S, VAN HOGEZAND R et al.: Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn's disease: a European multicenter trial. Gastroenterology (1999) 116(5):1029-1034.
28. 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. An important study demonstrating the efficacy of infliximab in the treatment of CD fistulae.
29. SANDBORN WJ, FEAGAN BG, HANAUER SB et al.: An engineered human antibody to TNF (CDP571) for active Crohn's disease: a randomized double-blind placebo-controlled trial. Gastroenterology (2001) 120(6):1330-1338.
30. D'HAENS G, SWIJSEN C, NOMAN M et al.: Etanercept in the treatment of active refractory Crohn's disease: a single-center pilot trial. Am. J. Gastroenterol. (2001) 96(9):2564-2568.
31. SANDBORN WJ, HANAUER SB, KATZ S et al.: Etanercept for active Crohn's disease: a randomized, double-blind, placebo-controlled trial. Gastroenterology (2001) 121(5):1088-1094.
32. SANDS BE, TREMAINE WJ, SANDBORN WJ et al.: Infliximab in the treatment of severe, steroid-refractory ulcerative colitis: a pilot study. Inflamm. Bowel Dis. (2001) 7(2):83-88.
33. CHEY WY: Infliximab for patients with refractory ulcerative colitis. Inflamm. Bowel Dis. (2001) 7(Suppl. 1):S30-S33.
34. EVANS RC, CLARKE L, HEATH P et al.: Treatment of ulcerative colitis with an engineered human anti-TNFalpha antibody CDP571. Aliment. Pharmacol. Ther. (1997) 11(6):1031-1035.
35. 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.
36. KIETZ DA, PEPMUELLER PH, MOORE TL: Therapeutic use of etanercept in polyarticular course juvenile idiopathic arthritis over a two year period. Ann. Rheum. Dis. (2002) 61(2):171-173.
37. OH CJ, DAS KM, GOTTLIEB AB: Treatment with anti-tumor necrosis factor alpha (TNF-alpha) monoclonal antibody dramatically decreases the clinical activity of psoriasis lesions. J. Am. Acad. Dermatol. (2000) 42(5 Pt 1):829-830.
38. KIRBY B, MARSLAND AM, CARMICHAEL AJ et al.: Successful treatment of severe recalcitrant psoriasis with combination infliximab and methotrexate. Clin. Exp. Dermatol. (2001) 26(1):27-29.
39. 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.
40. OGILVIE AL, ANTONI C, DECHANT C et al.: Treatment of psoriatic arthritis with antitumour necrosis factor-alpha antibody clears skin lesions of psoriasis resistant to treatment with methotrexate. Br. J. Dermatol. (2001) 144(3):587-589.
41. MEASE PJ, GOFFE BS, METZ J et al.: Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. Lancet (2000) 356(9227):385-390.
42. MEASE PJ: Tumour necrosis factor (TNF) in psoriatic arthritis: pathophysiology and treatment with TNF inhibitors. Ann. Rheum. Dis. (2002) 61(4):298-304.
43. BRANDT J, HAIBEL H, CORNELY D et al.: Successful treatment of active ankylosing spondylitis with the anti-tumor necrosis factor alpha monoclonal antibody infliximab. Arthritis Rheum. (2000) 43(6):1346-1352.
44. GORMAN JD, SACK KE, DAVIS JC: Etanercept in the treatment of ankylosing spondylitis: a randomized, double-blind, placebo-controlled study. Arthritis Rheum. (2000) 43(Suppl.):S403.
45. VAN BEN BOSCH F, BEATEN D, KRUITHOF F et al.: Treatment of active spondyloarthropathy with infliximab, the chimeric monoclonal antibody to tumour necrosis factor α. Ann. Rheum. Dis. (2001) 60 (Suppl):iii33-iii36.
46. ANDREAKOS E, TAYLOR PC, FELDMANN M: Monoclonal antibodies in immune and inflammatory diseases. Curr. Opin. Biotechnol. (2002) 13(6):615-20. A recent review of mAb-based therapeutics in the treatment of inflammatory diseases.
47. NO AUTHORS LISTED: TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study. The Lenercept Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group. Neurology (1999) 53(3):457-465.
48. VAN OOSTEN BW, BARKHOF F, TRUYEN L et al.: Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2. Neurology (1996) 47(6):1531-1534.
49. DREVLOW BE, LOVIS R, HAAG MA et al.: Recombinant human interleukin-1 receptor type I in the treatment of patients with active rheumatoid arthritis. Arthritis Rheum. (1996) 39(2):257-265.
50. 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.
51. 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.
52. WENDLING D, RACADOT E, WIJDENES J: Treatment of severe rheumatoid arthritis by anti-interleukin 6 monoclonal antibody. J. Rheumatol. (1993) 20(2):259-262.
53. YOSHIZAKI K, NISHIMOTO N, MIHARA M et al.: Therapy of rheumatoid arthritis by blocking IL-6 signal transduction with a humanized anti-IL-6 receptor antibody. Springer Semin. Immunopathol. (1998) 20(1-2):247-259.
54. LOHNER M, SCHWAB G, KRUEGER G: Clinical trial results: a fully human anti-IL-8 antibody in patients with moderate to severe psoriasis. J. Am. Acad. Dermatol. (2001) 44:P516.
55. GHORESCHI K, THOMAS P, BREIT S et al.: Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease. Nat. Med. (2003) 9(1):40-46.
56. VAN DEVENTER SJ, ELSON CO, FEDORAK RN: Multiple doses of intravenous interleukin 10 in steroidrefractory Crohn's disease. Crohn's Disease Study Group. Gastroenterology (1997) 113(2):383-389.
57. SCHREIBER S, FEDORAK RN, NIELSEN OH et al. Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease. Crohn's Disease IL-10 Cooperative Study Group. Gastroenterology (2000) 119(6):1461-1472.
58. FEDORAK RN, GANGL A, ELSON CO et al.: Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn's disease. The Interleukin 10 Inflammatory Bowel Disease Cooperative Study Group. Gastroenterology (2000) 119(6):1473-1482.
59. SCHREIBER S, FEDORAK RN, WILD G et al.: Safety, tolerance and efficacy of rHuIL-10 treatment in patients with mild/moderate active ulcerative colitis [abstract]. Gastroenterology (1998) 114:G4424.
60. ASADULLAH K, STERRY W, STEPHANEK K et al.: IL-10 is a key cytokine in psoriasis. Proof of principle by IL-10 therapy: a new therapeutic approach. J. Clin. Invest (1998) 101(4):783-794.
61. ASADULLAH K, DOCKE WD, EBELING M et al.: Interleukin 10 treatment of psoriasis: clinical results of a phase 2 trial. Arch. Dermatol. (1999) 135(2):187-192.
62. MCINNES IB, ILLEI GG, DANNING CL et al.: IL-10 improves skin disease and modulates endothelial activation and leukocyte effector function in patients with psoriatic arthritis. J. Immunol. (2001) 167(7):4075-4082.
63. TREPICCHIO WL, OZAWA M, WALTERS IB et al.: Interleukin-II therapy selectively downregulates type I cytokine proinflammatory pathways in psoriasis lesions. J. Clin. Invest. (1999) 104(11):1527-1537.
64. NUIJTEN MJ, ENGELFRIET P, DUIJN K et al.: A cost-cost study comparing etanercept with infliximab in rheumatoid arthritis. Pharmacoeconomics (2001) 19(10):1051-1064.
65. SHAKHOV AN, COLLART MA, VASSALLI P et al.: Kappa B-type enhancers are involved in lipopolysaccharide-mediated transcriptional activation of the tumor necrosis factor alpha gene in primary macrophages. J. Exp. Med. (1990) 171(1):35-47.
66. GOLDFELD AE, STROMINGER JL, DOYLE C: Human tumor necrosis factor alpha gene regulation in phorbol ester stimulated T and B cell lines. J. Exp. Med. (1991) 174(1):73-81.
67. MCCAFFREY PG, GOLDFELD AE, RAO A: The role of NFATp in cyclosporin A-sensitive tumor necrosis factor-alpha gene transcription. J. Biol. Chem. (1994) 269(48):30445-30450.
68. HAN J, BEUTLER B: The essential role of the UA-rich sequence in endotoxin-induced cachectin/TNF synthesis. Eur. Cytokine Netw. (1990) 1(2):71-75.
69. ANDREAKOS E, SMITH C, MONACO C et al.: I{kappa}B kinase 2 but not NF-{kappa}B-inducing kinase is essential for effective DC antigen presentation in the allogeneic mixed lymphocyte reaction. Blood (2002) 101(3):983-991.
70. BONDESON J, BROWNE KA, BRENNAN FM et al.: Selective regulation of cytokine induction by adenoviral gene transfer of IkappaBalpha into human macrophages: lipopolysaccharide-induced, but not zymosan-induced, proinflammatory cycokines are inhibited, but IL-10 is nuclear factor-kappaB independent. J. Immunol. (1999) 162(5):2939-2945.
71. SMITH C, ANDREAKOS E, CRAWLEY JB et al.: NF-kappaB-inducing kinase is dispensable for activation of NF-kappaB in inflammatory settings but essential for lymphotoxin beta receptor activation of NF-kappaB in primary human fibroblasts. J. Immunol. (2001) 167(10):5895-5903.
72. CONRON M, ANDREAKOS E, PANTELIDIS P et al.: Nuclear factor-kappaB activation in alveolar macrophages requires IkappaB kinase-beta, but not nuclear factor-kappaB inducing kinase. Am. J. Respir. Crit. Care Med (2002) 165(7):996-1004.
73. BRENNAN FM, HAYES AL, CIESIELSKI CJ et al.: Evidence that rheumatoid arthritis synovial T cells are similar to cytokine-activated T cells: involvement of phosphatidylinositol 3-kinase and nuclear factor kappaB pathways in tumor necrosis factor alpha production in rheumatoid arthritis. Arthritis Rheum. (2002) 46(1):31-41.
74. HAYES AL, SMITH C, FOXWELL BM et al.: CD45-induced tumor necrosis factor alpha production in monocytes is phosphatidylinositol 3-kinase-dependent and nuclear factor-kappaB-independent. J. Biol. Chem. (1999) 274(47):33455-33461.
75. BURAS JA, MONKS BG, FENTON MJ: The NF-beta A-binding element, not an overlapping NF-IL-6-binding element, is required for maximal IL-1 beta gene expression. J. Immunol. (1994) 152(9):4444-4454.
76. GRAY JG, CHANDRA G, CLAY WC et al.: A CRE/ATF-like site in the upstream regulatory sequence of the human interleukin 1 beta gene is necessary for induction in U937 and THP-1 monocytic cell lines. Mol. Cell Biol. (1993) 13(11):6678-6689.
77. SERKKOLA E, HURME M: Synergism between protein-kinase C and cAMP-dependent pathways in the expression of the interleukin-1 beta gene is mediated via the activator-protein-1 (AP-1) enhancer activity. Eur. J. Biochem. (1993) 213(1):243-249.
78. COGSWELL JP, GODLEVSKI MM, WISELY GB et al.: NF-kappa B regulates IL-1 beta transcription through a consensus NF-kappa B binding site and a nonconsensus CRE-like site. J. Immunol. (1994) 153(2):712-723.
79. ZHANG Y, ROM WN: Regulation of the interleukin-1 beta (IL-1 beta) gene by mycobacterial components and lipopolysaccharide is mediated by two nuclear factor-IL6 motifs. Mol. Cell Biol. (1993) 13(6):3831-3837.
80. GODAMBE SA, CHAPLIN DD, TAKOVA T et al.: Upstream NFIL-6-like site located within a DNase I hypersensitivity region mediates LPS-induced transcription of the murine interleukin-1 beta gene. J. Immunol. (1994) 153(1):143-152.
81. VANDEN BERGHE W, PLAISANCE S, BOONE E et al.: p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways are required for nuclear factor-kappaB p65 transactivation mediated by tumor necrosis factor. J. Biol. Chem. (1998) 273(6):3285-3290.
82. VANDEN BERGHE W, DE BOSSCHER K, BOONE E et al.: The nuclear factor-kappaB engages CBP/p300 and histone acetyltransferase activity for transcriptional activation of the interleukin-6 gene promoter. J. Biol. Chem. (1999) 274(45):32091-32098.
83. HOFFMANN E, DITTRICH-BREIHOLZ O, HOLTMANN H et al.: Multiple control of interleukin-8 gene expression. J. Leukoc. Biol. (2002) 72(5):847-855.
84. CIESIELSKI CJ, ANDREAKOS E, FOXWELL BM et al.: TNFalpha-induced macrophage chemokine secretion is more dependent on NF-kappaB expression than lipopolysaccharides-induced macrophage chemokine secretion. Eur. J. Immunol. (2002) 32(7):2037-2045.
85. ASAHARA H, ASANUMA M, OGAWA N et al.: High DNA-binding activity of transcription factor NF-kappa B in synovial membranes of patients with rheumatoid arthritis. Biochem. Mol. Biol. Int. (1995) 37(5):827-832.
86. HANDEL ML, MCMORROW LB, GRAVALLESE EM: Nuclear factor-kappa B in rheumatoid synovium. Localization of p50 and p65. Arthritis Rheum. (1995) 38(12):1762-1770.
87. MAROK R, WINYARD PG, COUMBE A et al.: Activation of the transcription factor nuclear factor-kappaB in human inflamed synovial tissue. Arthritis Rheum. (1996) 39(4):583-591.
88. FOXWELL B, BROWNE K, BONDESON J et al.: Efficient adenoviral infection with IkappaB alpha reveals that macrophage tumor necrosis factor alpha production in rheumatoid arthritis is NF-kappaB dependent. Proc. Natl. Acad. Sci. USA (1998) 95(14):8211-8215.
89. BONDESON J, FOXWELL B, BRENNAN F et al.: Defining therapeutic targets by using adenovirus: blocking NF-kappaB inhibits both inflammatory and destructive mechanisms in rheumatoid synovium but spares anti-inflammatory mediators. Proc. Natl. Acad. Sci. USA (1999) 96(10):5668-5673. Evidence that NF-κB is selectively involved in inflammatory and destructive processes in RA.
90. IOTSOVA V, CAAMANO J, LOY J et al.: Osteopetrosis in mice lacking NF-kappaB1 and NF-kappaB2. Nat. Med (1997) 3(11):1285-1289.
91. DE CROMBRUGGHE B, LEFEBVRE V, BEHRINGER RR et al.: Transcriptional mechanisms of chondrocyte differentiation. Matrix Biol. (2000) 19(5):389-394.
92. MURAKAMI S, LEFEBVRE V, DE CROMBRUGGHE B: Potent inhibition of the master chondrogenic factor Sox9 gene by interleukin-1 and tumor necrosis factor-alpha. J. Biol. Chem. (2000) 275(5):3687-3692.
93. HAN Z, BOYLE DL, MANNING AM et al.: AP-1 and NF-kappaB regulation in rheumatoid arthritis and murine collagen-induced arthritis. Autoimmunity (1998) 28(4):197-208.
94. MIAGKOV AV, KOVALENKO DV, BROWN CE et al.: NF-kappaB activation provides the potential link between inflammation and hyperplasia in the arthritic joint. Proc. Natl Acad. Sci. USA (1998) 95(23):13859-13864.
95. PALOMBELLA VJ, CONNER EM, FUSELER JW et al.: Role of the proteasome and NF-kappaB in streptococcal cell wall-induced polyarthritis. Proc. Natl Acad. Sci. USA (1998) 95(26):15671-15676.
96. TSAO PW, SUZUKI T, TOTSUKA R et al.: The effect of dexamethasone on the expression of activated NF-kappa B in adjuvant arthritis. Clin. Immunol. Immunopathol. (1997) 83(2):173-178.
97. FELDMANN M, ANDREAKOS E, SMITH C et al.: Is NF-kappaB a useful therapeutic target in rheumatoid arthritis? Ann. Rheum. Dis. (2002) 61(Suppl. 2): ii13-ii18.
98. NEURATH MF, PETTERSSON S, MEYER ZUM BUSCHENFELDE KH et al.: Local administration of antisense phosphorothioate oligonucleotides to the p65 subunit of NF-kappa B abrogates established experimental colitis in mice. Nat. Med. (1996) 2(9):998-1004.
99. NEURATH MF, PETTERSSON S: Predominant role of NF-kappa B p65 in the pathogenesis of chronic intestinal inflammation. Immunobiology (1997) 198(1-3):91-98.
100. ROGLER G, BRAND K, VOGL D et al.: Nuclear factor kappaB is activated in macrophages and epithelial cells of inflamed intestinal mucosa. Gastroenterology (1998) 115(2):357-369.
101. SCHREIBER S, NIKOLAUS S, HAMPE J: Activation of nuclear factor kappa B inflammatory bowel disease. Gut (1998) 42(4):477-484.
102. FUJIHARA SM, CLEAVELAND JS, GROSMAIRE LS et al.: A D-amino acid peptide inhibitor of NF-kappa B nuclear localization is efficacious in models of inflammatory disease. J. Immunol. (2000) 165(2):1004-1012.
103. DANNING CL, ILLEI GG, HITCHON C et al.: Macrophage-derived cytokine and nuclear factor kappaB p65 expression in synovial membrane and skin of patients with psoriatic arthritis. Arthritis Rheum. (2000) 43(6):1244-1256.
104. ZOLLNER TM, PODDA M, PIEN C et al.: Proteasome inhibition reduces superantigen-mediated T cell activation and the severity of psoriasis in a SCID-hu model. J. Clin. Invest. (2002) 109(5):671-679.
105. CONRON M, BONDESON J, PANTELIDIS P et al.: Alveolar macrophages and T cells from sarcoid, but not normal lung, are permissive to adenovirus infection and allow analysis of NF-kappa b-dependent signaling pathways. Am. J. Respir. Cell Mol. Biol. (2001) 25(2):141-149.
106. BRAND K, PAGE S, ROGLER G et al.: Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion. J. Clin. Invest. (1996) 97(7):1715-1722.
107. LANDRY DB, COUPER LL, BRYANT SR et al.: Activation of the NF-kappa B and I kappa B system in smooth muscle cells after rat arterial injury. Induction of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1. Am. J. Pathol. (1997) 151(4):1085-1095.
108. HAJRA L, EVANS AI, CHEN M et al.: The NF-kappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation. Proc. Natl Acad. Sci. USA (2000) 97(16):9052-9057.
109. BONETTI B, STEGAGNO C, CANNELLA B et al.: Activation of NF-kappaB and c-jun transcription factors in multiple sclerosis lesions. Implications for oligodendrocyte pathology. Am. J. Pathol. (1999) 155(5):1433-1438.
110. GVERIC D, KALTSCHMIDT C, CUZNER ML et al.: Transcription factor NF-kappaB and inhibitor I kappaBalpha are localized in macrophages in active multiple sclerosis lesions. J. Neuropathol. Exp. Neurol. (1998) 57(2):168-178.
111. PAHAN K, SCHMID M: Activation of nuclear factor-kB in the spinal cord of experimental allergic encephalomyelitis. Neurosci. Lett. (2000) 287(1):17-20.
112. HILLIARD B, SAMOILOVA EB, LIU TS et al.: Experimental autoimmune encephalomyelitis in NF-kappa B-deficient mice:roles of NF-kappa B in the activation and differentiation of autoreactive T cells. J. Immunol. (1999) 163(5):2937-2943.
113. ANDREAKOS E, UDALOVA I, SACRE S et al.: The role of NF-κB in inflammatory diseases. In: Nuclear Factor κB: Regulation and Role in Disease. Beyaert R (Ed), Kluwer Academic Publishers, Amsterdam (2003):297-325.
114. NIKOLAUS S, RAEDLER A, KUHBACKER T et al.: Mechanisms in failure of infliximab for Crohn's disease. Lancet (2000) 356(9240):1475-1479.
115. SWANTEK JL, COBB MH, GEPPERT TD: Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) is required for lipopolysaccharide stimulation of tumor necrosis factor alpha (TNF-alpha) translation: glucocorticoids inhibit TNF-alpha translation by blocking JNK/SAPK. Mol. Cell Biol. (1997) 17(11):6274-6282.
116. FOEY AD, PARRY SL, WILLIAMS LM et al.: Regulation of monocyte IL-10 synthesis by endogenous IL-1 and TNF-alpha: role of the p38 and p42/44 mitogen-activated protein kinases. J. Immunol. (1998) 160(2):920-928.
117. RUTAULT K, HAZZALIN CA, MAHADEVAN LC: Combinations of ERK and p38 MAPK inhibitors ablate tumor necrosis factor-alpha (TNF-alpha) mRNA induction. Evidence for selective destabilization of TNF-alpha transcripts. J. Biol. Chem. (2001) 276(9):6666-6674.
118. DEAN JL, BROOK M, CLARK AR et al.: p38 mitogen-activated protein kinase regulates cyclooxygenase-2 mRNA stability and transcription in lipopolysaccharide-treated human monocytes. J. Biol. Chem. (1999) 274(1):264-269.
119. RIDLEY SH, DEAN JL, SARSFIELD SJ et al.: A p38 MAP kinase inhibitor regulates stability of interleukin-1-induced cyclooxygenase-2 mRNA. FEBS Lett. (1998) 439(1-2):75-80.
120. CAIVANO M, COHEN P: Role of mitogen-activated protein kinase cascades in mediating lipopolysaccharide-stimulated induction of cyclooxygenase-2 and IL-1 beta in RAW264 macrophages. J. Immunol. (2000) 164(6):3018-3025.
121. HAN Z, BOYLE DL, AUPPERLE KR et al.: Jun N-terminal kinase in rheumatoid arthritis. J. Pharmacol. Exp. Ther. (1999) 291(1):124-130.
122. 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.
123. 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.
124. JACKSON JR, BOLOGNESE B, HILLEGASS L et al.: Pharmacological effects of SB 220025, a selective inhibitor of P38 mitogen-activated protein kinase, in angiogenesis and chronic inflammatory disease models. J. Pharmacol. Exp. Ther. (1998) 284(2):687-692.
125. 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.
126. WADSWORTH SA, CAVENDER DE, BEERS SA et al.: RWJ 67657, a potent, orally active inhibitor of p38 mitogen-activated protein kinase. J. Pharmacol. Exp. Ther. (1999) 291(2):680-687.
127. MCLAY LM, HALLEY F, SOUNESS JE et al.: The discovery of RPR 200765A, a p38 MAP kinase inhibitor displaying a good oral anti-arthritic efficacy. Bioorg. Med. Chem. (2001) 9(2):537-554.
128. FARZANEH-FAR A, DAVIES JD, BRAAM LA et al.: A polymorphism of the human matrix gamma-carboxyglutamic acid protein promoter alters binding of an activating protein-1 complex and is associated with altered transcription and serum levels. J. Biol. Chem. (2001) 76(35):32466-32473.
129. WAETZIG GH, SEEGERT D, ROSENSTIEL P et al.: p38 mitogen-activated protein kinase is activated and linked to TNF-alpha signaling in inflammatory bowel disease. J. Immunol. (2002) 168(10):5342-5351.
130. TEN HOVE T, VAN DEN BLINK B, PRONK I et al.: Dichotomal role of inhibition of p38 MAPK with SB 203580 in experimental colitis. Gut (2002) 50(4):507-512.
131. KONTOYIANNIS D, PASPARAKIS M, PIZARRO TT et al.: Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut-associated immunopathologies. Immunity (1999) 10(3):387-398.
132. KONTOYIANNIS D, BOULOUGOURIS G, MANOLOUKOS M et al.: Genetic dissection of the cellular pathways and signaling mechanisms in modeled tumor necrosis factor-induced Crohn's-like inflammatory bowel disease. J. Exp. Med. (2002) 196(12):1563-1574.
133. HOMMES D, VAN DEN BLINK B, PLASSE T et al.: Inhibition of stress-activated MAP kinases induces clinical improvement in moderate to severe Crohn's disease. Gastroenterology (2002) 122(1):7-14. A very important study demonstrating that MAPK inhibition results in significant clinical benefit in CD patients.
134. HAASE I, HOBBS RM, ROMERO MR et al.: A role for mitogen-activated protein kinase activation by integrins in the pathogenesis of psoriasis. J. Clin. Invest. (2001) 108(4):527-536.
135. UNDERWOOD DC, OSBORN RR, BOCHNOWICZ S et al.: SB 239063, a p38 MAPK inhibitor, reduces neutrophilia, inflammatory cytokines, MMP-9, and fibrosis in lung. Am. J. Physiol. Lung Cell Mol. Physiol. (2000) 279(5):L895-L902.
136. MATSUOKA H, ARAI T, MORI M et al.: A p38 MAPK inhibitor, FR-167653, ameliorates murine bleomycin-induced pulmonary fibrosis. Am. J. Physiol. Lung Cell Mol. Physiol. (2002) 283(1):L103-L112.
137. TORPHY TJ: Monoclonal antibodies: boundless potential, daunting challenges. Curr. Opin. Biotechnol. (2002) 13(6):589-591.