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Chapter 35 : Anti-TNF Therapy

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Abstract:

Tumor necrosis factor (TNF) is a member of the large family of cytokines; not hormones, but important local signaling molecules that transmit information from one cell to another ( ). Different cytokines convey different messages, but cytokines are key players in every important biological process, including immunity, inflammation, cell growth, migration, fibrosis, vascularization, etc. So it is not surprising that abnormalities of these key mediators, molecules that are important enough to be conserved through evolution, may be involved in disease processes. What might not have been predicted was that removal of a single upregulated cytokine can make a clinical difference. This is best documented for anti-TNF ( ) but is also true for blockade of interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-1. In this review, we will summarize the current state of knowledge about cytokine expression and dysregulation in rheumatoid arthritis (RA) and other diseases and the role of TNF, the great majority of which is produced by macrophages. The knowledge gained has impacted our understanding of and therapy for other diseases also, and by focusing on cytokines, major rate-limiting steps, and hence therapeutic targets, there are opportunities for planning of therapy for many unmet needs.

Citation: Udalova I, Monaco C, Nanchahal J, Feldmann M. 2017. Anti-TNF Therapy, p 637-648. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0022-2015
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References

/content/book/10.1128/9781555819194.chap35
1. Thomson AW,, Lotze MT (ed) . 2003. The Cytokine Handbook, 4th ed. Academic Press, San Diego, CA.
2. Feldmann M,, Maini RN . 2003. Lasker Clinical Medical Research Award. TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases. Nat Med 9 : 1245 1250.[PubMed] [CrossRef]
3. Klareskog L,, Catrina AI,, Paget S . 2009. Rheumatoid arthritis. Lancet 373 : 659 672.[PubMed] [CrossRef]
4. Wegner N,, Lundberg K,, Kinloch A,, Fisher B,, Malmström V,, Feldmann M,, Venables PJ . 2010. Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of rheumatoid arthritis. Immunol Rev 233 : 34 54.[PubMed] [CrossRef]
5. Harre U,, Georgess D,, Bang H,, Bozec A,, Axmann R,, Ossipova E,, Jakobsson PJ,, Baum W,, Nimmerjahn F,, Szarka E,, Sarmay G,, Krumbholz G,, Neumann E,, Toes R,, Scherer HU,, Catrina AI,, Klareskog L,, Jurdic P,, Schett G . 2012. Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Invest 122 : 1791 1802.[PubMed] [CrossRef]
6. Bell JI,, Todd JA,, McDevitt HO . 1989. The molecular basis of HLA-disease association. Adv Hum Genet 18 : 1 41.[PubMed] [CrossRef]
7. Klareskog L,, Forsum U,, Scheynius A,, Kabelitz D,, Wigzell H . 1982. Evidence in support of a self-perpetuating HLA-DR-dependent delayed-type cell reaction in rheumatoid arthritis. Proc Natl Acad Sci U S A 79 : 3632 3636.[PubMed] [CrossRef]
8. Bottazzo GF,, Pujol-Borrell R,, Hanafusa T,, Feldmann M . 1983. Role of aberrant HLA-DR expression and antigen presentation in induction of endocrine autoimmunity. Lancet 2 : 1115 1119.[PubMed] [CrossRef]
9. Sztein MB,, Steeg PS,, Johnson HM,, Oppenheim JJ . 1984. Regulation of human peripheral blood monocyte DR antigen expression in vitro by lymphokines and recombinant interferons. J Clin Invest 73 : 556 565.[PubMed] [CrossRef]
10. Sarvetnick N,, Shizuru J,, Liggitt D,, Martin L,, McIntyre B,, Gregory A,, Parslow T,, Stewart T . 1990. Loss of pancreatic islet tolerance induced by β-cell expression of interferon-γ. Nature 346 : 844 847.[PubMed] [CrossRef]
11. Londei M,, Lamb JR,, Bottazzo GF,, Feldmann M . 1984. Epithelial cells expressing aberrant MHC class II determinants can present antigen to cloned human T cells. Nature 312 : 639 641.[PubMed] [CrossRef]
12. Londei M,, Bottazzo GF,, Feldmann M . 1985. Human T-cell clones from autoimmune thyroid glands: specific recognition of autologous thyroid cells. Science 228 : 85 89.[PubMed] [CrossRef]
13. Erhardt CC,, Mumford PA,, Venables PJ,, Maini RN . 1989. Factors predicting a poor life prognosis in rheumatoid arthritis: an eight year prospective study. Ann Rheum Dis 48 : 7 13.[PubMed] [CrossRef]
14. Goeddel DV,, Aggarwal BB,, Gray PW,, Leung DW,, Nedwin GE,, Palladino MA,, Patton JS,, Pennica D,, Shepard HM,, Sugarman BJ,, Wong GH . 1986. Tumor necrosis factors: gene structure and biological activities. Cold Spring Harb Symp Quant Biol 51 : 597 609.[PubMed] [CrossRef]
15. Buchan G,, Barrett K,, Turner M,, Chantry D,, Maini RN,, Feldmann M . 1988. Interleukin-1 and tumour necrosis factor mRNA expression in rheumatoid arthritis: prolonged production of IL-1α. Clin Exp Immunol 73 : 449 455.[PubMed]
16. Brennan FM,, Chantry D,, Jackson A,, Maini R,, Feldmann M . 1989. Inhibitory effect of TNFα antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet 2 : 244 247.[PubMed] [CrossRef]
17. Wood NC,, Dickens E,, Symons JA,, Duff GW . 1992. In situ hybridization of interleukin-1 in CD14-positive cells in rheumatoid arthritis. Clin Immunol Immunopathol 62 : 295 300.[PubMed] [CrossRef]
18. Poubelle P,, Damon M,, Blotman F,, Dayer JM . 1985. Production of mononuclear cell factor by mononuclear phagocytes from rheumatoid synovial fluid. J Rheumatol 12 : 412 417.[PubMed]
19. Xu WD,, Firestein GS,, Taetle R,, Kaushansky K,, Zvaifler NJ . 1989. Cytokines in chronic inflammatory arthritis. II. Granulocyte-macrophage colony-stimulating factor in rheumatoid synovial effusions. J Clin Invest 83 : 876 882.[PubMed] [CrossRef]
20. Feldmann M,, Brennan FM,, Maini RN . 1996. Role of cytokines in rheumatoid arthritis. Annu Rev Immunol 14 : 397 440.[PubMed] [CrossRef]
21. Feldmann M,, Easten A . 1971. The relationship between antigenic structure and the requirement for thymus-derived cells in the immune response. J Exp Med 134 : 103 119.[PubMed] [CrossRef]
22. Fong Y,, Tracey KJ,, Moldawer LL,, Hesse DG,, Manogue KB,, Kenney JS,, Lee AT,, Kuo GC,, Allison AC,, Lowry SF,, Cerami A . 1989. Antibodies to cachectin/tumor necrosis factor reduce interleukin 1β and interleukin 6 appearance during lethal bacteremia. J Exp Med 170 : 1627 1633.[PubMed] [CrossRef]
23. Haworth C,, Brennan FM,, Chantry D,, Turner M,, Maini RN,, Feldmann M . 1991. Expression of granulocyte-macrophage colony-stimulating factor in rheumatoid arthritis: regulation by tumor necrosis factor-α. Eur J Immunol 21 : 2575 2579.[PubMed] [CrossRef]
24. Butler DM,, Maini RN,, Feldmann M,, Brennan FM . 1995. Modulation of proinflammatory cytokine release in rheumatoid synovial membrane cell cultures. Comparison of monoclonal anti TNF-α antibody with the interleukin-1 receptor antagonist. Eur Cytokine Netw 6 : 225 230.[PubMed]
25. Williams RO,, Feldmann M,, Maini RN . 1992. Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. Proc Natl Acad Sci U S A 89 : 9784 9788.[PubMed] [CrossRef]
26. Beutler B,, Cerami A . 1988. Cachectin, cachexia, and shock. Annu Rev Med 39 : 75 83.[PubMed] [CrossRef]
27. Elliott MJ,, Maini RN,, Feldmann M,, Long-Fox A,, Charles P,, Katsikis P,, Brennan FM,, Walker J,, Bijl H,, Ghrayeb J,, Woody J . 1993. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor α. Arthritis Rheum 36 : 1681 1690.[PubMed] [CrossRef]
28. Elliott MJ,, Maini RN,, Feldmann M,, Long-Fox A,, Charles P,, Bijl H,, Woody JN . 1994. Repeated therapy with monoclonal antibody to tumour necrosis factor α (cA2) in patients with rheumatoid arthritis. Lancet 344 : 1125 1127.[PubMed] [CrossRef]
29. Elliott MJ,, Maini RN,, Feldmann M,, Kalden JR,, Antoni C,, Smolen JS,, Leeb B,, Breedveld FC,, Macfarlane JD,, Bijl H,, Woody JN . 1994. Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor α (cA2) versus placebo in rheumatoid arthritis. Lancet 344 : 1105 1110.[CrossRef]
30. Maini RN,, Breedveld FC,, Kalden JR,, Smolen JS,, Davis D,, Macfarlane JD,, Antoni C,, Leeb B,, Elliott MJ,, Woody JN,, Schaible TF,, Feldmann M . 1998. 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 41 : 1552 1563.[PubMed] [CrossRef]
31. Weinblatt ME,, Kremer JM,, Bankhurst AD,, Bulpitt KJ,, Fleischmann RM,, Fox RI,, Jackson CG,, Lange M,, Burge DJ . 1999. A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 340 : 253 259.[PubMed] [CrossRef]
32. Weisman MH,, Moreland LW,, Furst DE,, Weinblatt ME,, Keystone EC,, Paulus HE,, Teoh LS,, Velagapudi RB,, Noertersheuser PA,, Granneman GR,, Fischkoff SA,, Chartash EK . 2003. Efficacy, pharmacokinetic, and safety assessment of adalimumab, a fully human anti-tumor necrosis factor-alpha monoclonal antibody, in adults with rheumatoid arthritis receiving concomitant methotrexate: a pilot study. Clin Ther 25 : 1700 1721.[PubMed] [CrossRef]
33. Charles P,, Elliott MJ,, Davis D,, Potter A,, Kalden JR,, Antoni C,, Breedveld FC,, Smolen JS,, Eberl G,, Woody JN,, Feldmann M,, Maini RN . 1999. Regulation of cytokines, cytokine inhibitors, and acute phase-proteins following anti-TNF-α therapy in rheumatoid arthritis. J Immunol 163 : 1521 1528.[PubMed]
34. Feldmann M,, Maini RN . 2001. Anti-TNFα therapy of rheumatoid arthritis: what have we learned? Annu Rev Immunol 19 : 163 196.[PubMed] [CrossRef]
35. Paleolog EM . 2002. Angiogenesis in rheumatoid arthritis. Arthritis Res 4( Suppl 3) : S81 S90.[PubMed] [CrossRef]
36. Rodkey LS . 1974. Studies of idiotypic antibodies. Production and characterization of autoantiidiotypic antisera. J Exp Med 139 : 712 720.[PubMed] [CrossRef]
37. Oudin J,, Michel M . 1969. Idiotypy of rabbit antibodies. II. Comparison of idiotypy of various kinds of antibodies formed in the same rabbits against Salmonella Typhi. J Exp Med 130 : 619 642.[PubMed] [CrossRef]
38. Mitchison NA . 1964. Induction of immunological paralysis in two zones of dosage. Proc R Soc Lond B Biol Sci 161 : 275 292.[PubMed] [CrossRef]
39. Golub ES,, Weigle WO . 1969. Studies on the induction of immunologic unresponsiveness. 3. Antigen form and mouse strain variation. J Immunol 102 : 389 396.[PubMed]
40. Feldmann M,, Maini RN . 2001. Anti-TNFα therapy of rheumatoid arthritis: what have we learned? Annu Rev Immunol 19 : 163 196.[PubMed] [CrossRef]
41. Pascual-Salcedo D,, Plasencia C,, Ramiro S,, Nuño L,, Bonilla G,, Nagore D,, Ruiz Del Agua A,, Martínez A,, Aarden L,, Martín-Mola E,, Balsa A . 2011. Influence of immunogenicity on the efficacy of long-term treatment with infliximab in rheumatoid arthritis. Rheumatology (Oxford) 50 : 1445 1452.[PubMed] [CrossRef]
42. Askling J,, Fored CM,, Brandt L,, Baecklund E,, Bertilsson L,, Cöster L,, Geborek P,, Jacobsson LT,, Lindblad S,, Lysholm J,, Rantapää-Dahlqvist S,, Saxne T,, Romanus V,, Klareskog L,, Feltelius N . 2005. Risk and case characteristics of tuberculosis in rheumatoid arthritis associated with tumor necrosis factor antagonists in Sweden. Arthritis Rheum 52 : 1986 1992.[PubMed] [CrossRef]
43. Hashimoto A,, Matsui T . 2015. Risk of serious infection in patients with rheumatoid arthritis. Nihon Rinsho Meneki Gakkai Kaishi 38 : 109 115. (In Japanese.)[PubMed] [CrossRef]
44. Listing J,, Gerhold K,, Zink A . 2013. The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment. Rheumatology (Oxford) 52 : 53 61.[PubMed] [CrossRef]
45. Smolen JS,, Aletaha D . 2013. Forget personalised medicine and focus on abating disease activity. Ann Rheum Dis 72 : 3 6.[PubMed] [CrossRef]
46. Feldmann M,, Maini RN . 2015. Can we get closer to a cure for rheumatoid arthritis? Arthritis Rheumatol 67 : 2283 2291.[PubMed] [CrossRef]
47. Sabin CA . 2013. Do people with HIV infection have a normal life expectancy in the era of combination antiretroviral therapy? BMC Med 11 : 251 257.[PubMed] [CrossRef]
48. Genovese MC,, Cohen S,, Moreland L,, Lium D,, Robbins S,, Newmark R,, Bekker P , 20000223 Study Group . 2004. Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate. Arthritis Rheum 50 : 1412 1419.[PubMed] [CrossRef]
49. Weinblatt M,, Schiff M,, Goldman A,, Kremer J,, Luggen M,, Li T,, Chen D,, Becker JC . 2007. Selective costimulation modulation using abatacept in patients with active rheumatoid arthritis while receiving etanercept: a randomised clinical trial. Ann Rheum Dis 66 : 228 234.[PubMed] [CrossRef]
50. Aletaha D,, Funovits J,, Smolen JS . 2011. Physical disability in rheumatoid arthritis is associated with cartilage damage rather than bone destruction. Ann Rheum Dis 70 : 733 739.[PubMed] [CrossRef]
51. Kaneko K,, Williams RO,, Dransfield DT,, Nixon AE,, Sandison A,, Itoh Y . 2016. Selective inhibition of membrane type 1 matrix metalloproteinase abrogates progression of experimental inflammatory arthritis: synergy with tumor necrosis factor blockade. Arthritis Rheumatol 68 : 521 531.[PubMed] [CrossRef]
52. Grivennikov SI,, Tumanov AV,, Liepinsh DJ,, Kruglov AA,, Marakusha BI,, Shakhov AN,, Murakami T,, Drutskaya LN,, Förster I,, Clausen BE,, Tessarollo L,, Ryffel B,, Kuprash DV,, Nedospasov SA . 2005. Distinct and nonredundant in vivo functions of TNF produced by T cells and macrophages/neutrophils: protective and deleterious effects. Immunity 22 : 93 104.[CrossRef]
53. Tak PP,, Bresnihan B . 2000. The pathogenesis and prevention of joint damage in rheumatoid arthritis: advances from synovial biopsy and tissue analysis. Arthritis Rheum 43 : 2619 2633.[PubMed] [CrossRef]
54. Smeets TJ,, Kraan MC,, Galjaard S,, Youssef PP,, Smith MD,, Tak PP . 2001. Analysis of the cell infiltrate and expression of matrix metalloproteinases and granzyme B in paired synovial biopsy specimens from the cartilage-pannus junction in patients with RA. Ann Rheum Dis 60 : 561 565.[PubMed] [CrossRef]
55. Mulherin D,, Fitzgerald O,, Bresnihan B . 1996. Synovial tissue macrophage populations and articular damage in rheumatoid arthritis. Arthritis Rheum 39 : 115 124.[PubMed] [CrossRef]
56. Barrera P,, Blom A,, van Lent PL,, van Bloois L,, Beijnen JH,, van Rooijen N,, de Waal Malefijt MC,, van de Putte LB,, Storm G,, van den Berg WB . 2000. Synovial macrophage depletion with clodronate-containing liposomes in rheumatoid arthritis. Arthritis Rheum 43 : 1951 1959.[PubMed] [CrossRef]
57. Haringman JJ,, Gerlag DM,, Zwinderman AH,, Smeets TJ,, Kraan MC,, Baeten D,, McInnes IB,, Bresnihan B,, Tak PP . 2005. Synovial tissue macrophages: a sensitive biomarker for response to treatment in patients with rheumatoid arthritis. Ann Rheum Dis 64 : 834 838.[PubMed] [CrossRef]
58. Hamilton JA . 2008. Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol 8 : 533 544.[PubMed] [CrossRef]
59. Gordon S,, Taylor PR . 2005. Monocyte and macrophage heterogeneity. Nat Rev Immunol 5 : 953 964.[PubMed] [CrossRef]
60. Cook AD,, Braine EL,, Campbell IK,, Rich MJ,, Hamilton JA . 2001. 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 3 : 293 298.[PubMed] [CrossRef]
61. Krausgruber T,, Blazek K,, Smallie T,, Alzabin S,, Lockstone H,, Sahgal N,, Hussell T,, Feldmann M,, Udalova IA . 2011. IRF5 promotes inflammatory macrophage polarization and T H1-T H17 responses. Nat Immunol 12 : 231 238.[PubMed] [CrossRef]
62. Krausgruber T,, Saliba D,, Ryzhakov G,, Lanfrancotti A,, Blazek K,, Udalova IA . 2010. IRF5 is required for late-phase TNF secretion by human dendritic cells. Blood 115 : 4421 4430.[PubMed] [CrossRef]
63. Saliba DG,, Heger A,, Eames HL,, Oikonomopoulos S,, Teixeira A,, Blazek K,, Androulidaki A,, Wong D,, Goh FG,, Weiss M,, Byrne A,, Pasparakis M,, Ragoussis J,, Udalova IA . 2014. IRF5:RelA interaction targets inflammatory genes in macrophages. Cell Rep 8 : 1308 1317.[PubMed] [CrossRef]
64. Tamura T,, Yanai H,, Savitsky D,, Taniguchi T . 2008. The IRF family transcription factors in immunity and oncogenesis. Annu Rev Immunol 26 : 535 584.[PubMed] [CrossRef]
65. Weiss M,, Blazek K,, Byrne AJ,, Perocheau DP,, Udalova IA . 2013. IRF5 is a specific marker of inflammatory macrophages in vivo . Mediators Inflamm 2013 : 245804. doi:10.1155/2013/245804. [CrossRef]
66. Stahl EA,, Raychaudhuri S,, Remmers EF,, Xie G,, Eyre S,, Thomson BP,, Li Y,, Kurreeman FA,, Zhernakova A,, Hinks A,, Guiducci C,, Chen R,, Alfredsson L,, Amos CI,, Ardlie KG,; BIRAC Consortium, Barton A,, Bowes J,, Brouwer E,, Burtt NP,, Catanese JJ,, Coblyn J,, Coenen MJ,, Costenbader KH,, Criswell LA,, Crusius JB,, Cui J,, de Bakker PI,, De Jager PL,, Ding B,, Emery P,, Flynn E,, Harrison P,, Hocking LJ,, Huizinga TW,, Kastner DL,, Ke X,, Lee AT,, Liu X,, Martin P,, Morgan AW,, Padyukov L,, Posthumus MD,, Radstake TR,, Reid DM,, Seielstad M,, Seldin MF,, Shadick NA,, Steer S,, Tak PP , , et al . 2010. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet 42 : 508 514.[PubMed] [CrossRef]
67. Dawidowicz K,, Allanore Y,, Guedj M,, Pierlot C,, Bombardieri S,, Balsa A,, Westhovens R,, Barrera P,, Alves H,, Teixeira VH,, Petit-Teixeira E,, van de Putte L,, van Riel P,, Prum B,, Bardin T,, Meyer O,, Cornélis F,, Dieudé P , ECRAF . 2011. The interferon regulatory factor 5 gene confers susceptibility to rheumatoid arthritis and influences its erosive phenotype. Ann Rheum Dis 70 : 117 121.[PubMed] [CrossRef]
68. Courties G,, Heidt T,, Sebas M,, Iwamoto Y,, Jeon D,, Truelove J,, Tricot B,, Wojtkiewicz G,, Dutta P,, Sager HB,, Borodovsky A,, Novobrantseva T,, Klebanov B,, Fitzgerald K,, Anderson DG,, Libby P,, Swirski FK,, Weissleder R,, Nahrendorf M . 2014. In vivo silencing of the transcription factor IRF5 reprograms the macrophage phenotype and improves infarct healing. J Am Coll Cardiol 63 : 1556 1566.[PubMed] [CrossRef]
69. Hansson GK,, Jonasson L,, Holm J,, Claesson-Welsh L . 1986. Class II MHC antigen expression in the atherosclerotic plaque: smooth muscle cells express HLA-DR, HLA-DQ and the invariant gamma chain. Clin Exp Immunol 64 : 261 268.[PubMed]
70. Barath P,, Fishbein MC,, Cao J,, Berenson J,, Helfant RH,, Forrester JS . 1990. Detection and localization of tumor necrosis factor in human atheroma. Am J Cardiol 65 : 297 302.[PubMed] [CrossRef]
71. Bevilacqua MP,, Pober JS,, Majeau GR,, Fiers W,, Cotran RS,, Gimbrone MA Jr . 1986. Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: characterization and comparison with the actions of interleukin 1. Proc Natl Acad Sci U S A 83 : 4533 4537.[PubMed] [CrossRef]
72. Elhage R,, Maret A,, Pieraggi MT,, Thiers JC,, Arnal JF,, Bayard F . 1998. Differential effects of interleukin-1 receptor antagonist and tumor necrosis factor binding protein on fatty-streak formation in apolipoprotein E-deficient mice. Circulation 97 : 242 244.[PubMed] [CrossRef]
73. Brånén L,, Hovgaard L,, Nitulescu M,, Bengtsson E,, Nilsson J,, Jovinge S . 2004. Inhibition of tumor necrosis factor-α reduces atherosclerosis in apolipoprotein E knockout mice. Arterioscler Thromb Vasc Biol 24 : 2137 2142.[PubMed] [CrossRef]
74. Ohta H,, Wada H,, Niwa T,, Kirii H,, Iwamoto N,, Fujii H,, Saito K,, Sekikawa K,, Seishima M . 2005. Disruption of tumor necrosis factor-alpha gene diminishes the development of atherosclerosis in ApoE-deficient mice. Atherosclerosis 180 : 11 17.[PubMed] [CrossRef]
75. Ridker PM,, Rifai N,, Pfeffer M,, Sacks F,, Lepage S,, Braunwald E . 2000. Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction. Circulation 101 : 2149 2153.[PubMed] [CrossRef]
76. Monaco C,, Andreakos E,, Kiriakidis S,, Mauri C,, Bicknell C,, Foxwell B,, Cheshire N,, Paleolog E,, Feldmann M . 2004. Canonical pathway of nuclear factor kappa B activation selectively regulates proinflammatory and prothrombotic responses in human atherosclerosis. Proc Natl Acad Sci U S A 101 : 5634 5639.[PubMed] [CrossRef]
77. Anker SD,, Coats AJ . 2002. How to RECOVER from RENAISSANCE? The significance of the results of RECOVER, RENAISSANCE, RENEWAL and ATTACH. Int J Cardiol 86 : 123 130.[PubMed] [CrossRef]
78. Coletta AP,, Clark AL,, Banarjee P,, Cleland JG . 2002. Clinical trials update: RENEWAL (RENAISSANCE and RECOVER) and ATTACH. Eur J Heart Fail 4 : 559 561.[PubMed] [CrossRef]
79. Chung ES,, Packer M,, Lo KH,, Fasanmade AA,, Willerson JT , Anti-TNF Therapy Against Congestive Heart Failure Investigators . 2003. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation 107 : 3133 3140.[PubMed] [CrossRef]
80. Raggatt LJ,, Wullschleger ME,, Alexander KA,, Wu AC,, Millard SM,, Kaur S,, Maugham ML,, Gregory LS,, Steck R,, Pettit AR . 2014. Fracture healing via periosteal callus formation requires macrophages for both initiation and progression of early endochondral ossification. Am J Pathol 184 : 3192 3204.[PubMed] [CrossRef]
81. Lucas T,, Waisman A,, Ranjan R,, Roes J,, Krieg T,, Müller W,, Roers A,, Eming SA . 2010. Differential roles of macrophages in diverse phases of skin repair. J Immunol 184 : 3964 3977.[PubMed] [CrossRef]
82. Sindrilaru A,, Scharffetter-Kochanek K . 2013. Disclosure of the Culprits: Macrophages-Versatile Regulators of Wound Healing. Adv Wound Care (New Rochelle) 2 : 357 368.[PubMed] [CrossRef]
83. Novak ML,, Koh TJ . 2013. Macrophage phenotypes during tissue repair. J Leukoc Biol 93 : 875 881.[PubMed] [CrossRef]
84. Murray PJ,, Wynn TA . 2011. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 11 : 723 737.[PubMed] [CrossRef]
85. Varga J,, Pasche B . 2009. Transforming growth factor beta as a therapeutic target in systemic sclerosis. Nat Rev Rheumatol 5 : 200 206.[PubMed] [CrossRef]
86. Hawinkels LJ,, Ten Dijke P . 2011. Exploring anti-TGF-β therapies in cancer and fibrosis. Growth Factors 29 : 140 152.[PubMed] [CrossRef]
87. Dolmans GH,, Werker PM,, Hennies HC,, Furniss D,, Festen EA,, Franke L,, Becker K,, van der Vlies P,, Wolffenbuttel BH,, Tinschert S,, Toliat MR,, Nothnagel M,, Franke A,, Klopp N,, Wichmann HE,, Nürnberg P,, Giele H,, Ophoff RA,, Wijmenga C , Dutch Dupuytren Study Group, German Dupuytren Study Group, LifeLines Cohort Study, BSSH-GODD Consortium . 2011. Wnt signaling and Dupuytren’s disease. N Engl J Med 365 : 307 317.[PubMed] [CrossRef]
88. Verjee LS,, Verhoekx JS,, Chan JK,, Krausgruber T,, Nicolaidou V,, Izadi D,, Davidson D,, Feldmann M,, Midwood KS,, Nanchahal J . 2013. Unraveling the signaling pathways promoting fibrosis in Dupuytren’s disease reveals TNF as a therapeutic target. Proc Natl Acad Sci U S A 110 : E928 E937.[PubMed] [CrossRef]
89. Wick G,, Grundtman C,, Mayerl C,, Wimpissinger TF,, Feichtinger J,, Zelger B,, Sgonc R,, Wolfram D . 2013. The immunology of fibrosis. Annu Rev Immunol 31 : 107 135.[PubMed] [CrossRef]
90. Edwards AM , , et al, SGC Open Source Target-Discovery Partnership . 2015. Preclinical target validation using patient-derived cells. Nat Rev Drug Discov 14 : 149 150.[PubMed] [CrossRef]
91. Glass GE,, Chan JK,, Freidin A,, Feldmann M,, Horwood NJ,, Nanchahal J . 2011. TNF-alpha promotes fracture repair by augmenting the recruitment and differentiation of muscle-derived stromal cells. Proc Natl Acad Sci U S A 108 : 1585 1590.[PubMed] [CrossRef]
92. Chan JK,, Glass GE,, Ersek A,, Freidin A,, Williams GA,, Gowers K,, Espirito Santo AI,, Jeffery R,, Otto WR,, Poulsom R,, Feldmann M,, Rankin SM,, Horwood NJ,, Nanchahal J . 2015. Low-dose TNF augments fracture healing in normal and osteoporotic bone by up-regulating the innate immune response. EMBO Mol Med 7 : 547 561.[PubMed] [CrossRef]

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