![conference banner](/images/conference-banner.jpeg)
摘要
类风湿关节炎(RA)是一种全身性、慢性、自身免疫性、炎症性疾病,影响大小滑膜关节的对称模式。RA一开始是关节疼痛的炎症,导致关节僵硬、关节破坏,并进一步恶化病情,对关节造成永久性不可逆损伤,使其残疾。在全球范围内,约有120万例风湿性关节炎病例。尽管有各种可用的治疗和药理学药物对抗风湿性关节炎,但没有一种治疗能保证完全治愈。深入了解细胞因子和白细胞介素在RA疾病发病机制中的作用,有助于开发它们来开发新的治疗策略。本文综述了RA的发病机制,并简要概述了在疾病进展中发挥重要作用的细胞因子。我们还讨论了白细胞介素在RA中的可能作用,这可能有助于未来的研究人员探索它们,以确定新的治疗药物。
关键词: 类风湿关节炎,细胞因子,白细胞介素,TNF-α, IL-1
[1]
Smolen JS, Aletaha D, Barton A, et al. Rheumatoid arthritis. Nat Rev Dis Primers 2018; 4: 18001.
[2]
Johnson KJ, Sanchez HN, Schoenbrunner N. Defining response to TNF-inhibitors in rheumatoid arthritis: the negative impact of anti-TNF cycling and the need for a personalized medicine approach to identify primary non-responders. Clin Rheumatol 2019; 38(11): 2967-76.
[http://dx.doi.org/10.1007/s10067-019-04684-1] [PMID: 31520227]
[http://dx.doi.org/10.1007/s10067-019-04684-1] [PMID: 31520227]
[3]
Handa R, Rao URK, Lewis JFM, Rambhad G, Shiff S, Ghia CJ. Literature review of rheumatoid arthritis in India. Int J Rheum Dis 2016; 19(5): 440-51.
[http://dx.doi.org/10.1111/1756-185X.12621] [PMID: 26171649]
[http://dx.doi.org/10.1111/1756-185X.12621] [PMID: 26171649]
[4]
Rudan I, Sidhu S, Papana A, et al. Global Health Epidemiology Reference Group (GHERG). Prevalence of rheumatoid arthritis in low- and middle-income countries: A systematic review and analysis. J Glob Health 2015; 5(1): 010409.
[PMID: 25969732]
[PMID: 25969732]
[6]
Alamanos Y, Voulgari PV, Drosos AA. Incidence and prevalence of rheumatoid arthritis, based on the 1987 American College of Rheumatology criteria: a systematic review. Semin Arthritis Rheum 2006; 36(3): 182-8.
[http://dx.doi.org/10.1016/j.semarthrit.2006.08.006] [PMID: 17045630]
[http://dx.doi.org/10.1016/j.semarthrit.2006.08.006] [PMID: 17045630]
[7]
Raychaudhuri S, Sandor C, Stahl EA, et al. Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nat Genet 2012; 44(3): 291-6.
[http://dx.doi.org/10.1038/ng.1076] [PMID: 22286218]
[http://dx.doi.org/10.1038/ng.1076] [PMID: 22286218]
[8]
Ting YT, Petersen J, Ramarathinam SH, et al. The interplay between citrullination and HLA-DRB1 polymorphism in shaping peptide binding hierarchies in rheumatoid arthritis. J Biol Chem 2018; 293(9): 3236-51.
[http://dx.doi.org/10.1074/jbc.RA117.001013] [PMID: 29317506]
[http://dx.doi.org/10.1074/jbc.RA117.001013] [PMID: 29317506]
[9]
Hedström AK, Rönnelid J, Klareskog L, Alfredsson L. Complex relationships of smoking, hla-drb1 genes, and serologic profiles in patients with early rheumatoid arthritis: update from a swedish population-based case-control study. Arthritis Rheumatol 2019; 71(9): 1504-11.
[http://dx.doi.org/10.1002/art.40852] [PMID: 30742363]
[http://dx.doi.org/10.1002/art.40852] [PMID: 30742363]
[10]
Manasson J, Blank RB, Scher JU. The microbiome in rheumatology: Where are we and where should we go? Ann Rheum Dis 2020; 79(6): 727-33.
[PMID: 32332073]
[PMID: 32332073]
[11]
Dar L, Tiosano S, Watad A, et al. Are obesity and rheumatoid arthritis interrelated? Int J Clin Pract
[http://dx.doi.org/10.1111/ijcp.13045]
[http://dx.doi.org/10.1111/ijcp.13045]
[12]
Farquhar H, Vassallo R, Edwards AL, Matteson EL. Pulmonary complications of rheumatoid arthritis. Semin Respir Crit Care Med 2019; 40(2): 194-207.
[http://dx.doi.org/10.1055/s-0039-1683995] [PMID: 31137060]
[http://dx.doi.org/10.1055/s-0039-1683995] [PMID: 31137060]
[14]
Safiri S, Kolahi AA, Hoy D, et al. Global, regional and national burden of rheumatoid arthritis 1990-2017: a systematic analysis of the Global Burden of Disease study 2017. Ann Rheum Dis 2019; 78(11): 1463-71.
[http://dx.doi.org/10.1136/annrheumdis-2019-215920] [PMID: 31511227]
[http://dx.doi.org/10.1136/annrheumdis-2019-215920] [PMID: 31511227]
[15]
Bullock J, Rizvi SAA, Saleh AM, et al. Rheumatoid arthritis: A brief overview of the treatment. Med Princ Pract 2018; 27(6): 501-7.
[http://dx.doi.org/10.1159/000493390] [PMID: 30173215]
[http://dx.doi.org/10.1159/000493390] [PMID: 30173215]
[16]
Sizova L. Approaches to the treatment of early rheumatoid arthritis with disease-modifying antirheumatic drugs. Br J Clin Pharmacol 2008; 66(2): 173-8.
[http://dx.doi.org/10.1111/j.1365-2125.2008.03222.x] [PMID: 18537958]
[http://dx.doi.org/10.1111/j.1365-2125.2008.03222.x] [PMID: 18537958]
[17]
Jin Y, Desai RJ, Liu J, et al. Factors associated with initial or subsequent choice of biologic disease-modifying antirheumatic drugs for treatment of rheumatoid arthritis. Arthritis Res Ther 2017; 15: 159.
[http://dx.doi.org/10.1186/s13075-017-1366-1]
[http://dx.doi.org/10.1186/s13075-017-1366-1]
[18]
Benjamin O, Bansal P, Goyal A, et al. Disease Modifying Anti-Rheumatic Drugs (DMARD) https://www.ncbi.nlm.nih.gov/books/NBK507863/2019.
[19]
Kean WF, Buchanan WW. The use of NSAIDs in rheumatic disorders 2005: a global perspective. Inflammopharmacology 2005; 13(4): 343-70.
[http://dx.doi.org/10.1163/156856005774415565] [PMID: 16354389]
[http://dx.doi.org/10.1163/156856005774415565] [PMID: 16354389]
[20]
Crofford LJ. Use of NSAIDs in treating patients with arthritis. Arthritis Res Ther 2013; 15(Suppl. 3): S2.
[http://dx.doi.org/10.1186/ar4174] [PMID: 24267197]
[http://dx.doi.org/10.1186/ar4174] [PMID: 24267197]
[21]
RA and Corticosteroids: What is the Role of Steroids in Arthritis Treatment? RheumatoidArthritis https://www.rheumatoidarthritis.org/treatment/medications/corticosteroids/
[22]
Dennison EM, Cooper C. Corticosteroids in rheumatoid arthritis. BMJ 1998; 316(7134): 789-90.
[http://dx.doi.org/10.1136/bmj.316.7134.789] [PMID: 9549442]
[http://dx.doi.org/10.1136/bmj.316.7134.789] [PMID: 9549442]
[23]
Gøtzsche PC, Johansen HK. Meta-analysis of short-term low dose prednisolone versus placebo and non-steroidal anti-inflammatory drugs in rheumatoid arthritis. BMJ 1998; 316(7134): 811-8.
[http://dx.doi.org/10.1136/bmj.316.7134.811] [PMID: 9549450]
[http://dx.doi.org/10.1136/bmj.316.7134.811] [PMID: 9549450]
[24]
Raza K, Holers VM, Gerlag D. Nomenclature for the Phases of the Development of Rheumatoid Arthritis. Clin Ther 2019; 41(7): 1279-85.
[http://dx.doi.org/10.1016/j.clinthera.2019.04.013] [PMID: 31196657]
[http://dx.doi.org/10.1016/j.clinthera.2019.04.013] [PMID: 31196657]
[25]
Tracy A, Buckley CD, Raza K. Pre-symptomatic autoimmunity in rheumatoid arthritis: when does the disease start? Semin Immunopathol 2017; 39(4): 423-35.
[http://dx.doi.org/10.1007/s00281-017-0620-6] [PMID: 28337522]
[http://dx.doi.org/10.1007/s00281-017-0620-6] [PMID: 28337522]
[26]
Guo Q, Wang Y, Xu D, et al. Rheumatoid arthritis: Pathological mechanisms and modern pharmacologic therapies. Bone Research 2018; 15(6)
[27]
van de Sande MGH, de Hair MJH, van der Leij C, et al. Different stages of rheumatoid arthritis: features of the synovium in the preclinical phase. Ann Rheum Dis 2011; 70(5): 772-7.
[http://dx.doi.org/10.1136/ard.2010.139527] [PMID: 21177292]
[http://dx.doi.org/10.1136/ard.2010.139527] [PMID: 21177292]
[28]
Catrina AI, Svensson CI, Malmström V, Schett G, Klareskog L. Mechanisms leading from systemic autoimmunity to joint-specific disease in rheumatoid arthritis. Nat Rev Rheumatol 2017; 13(2): 79-86.
[http://dx.doi.org/10.1038/nrrheum.2016.200] [PMID: 27974851]
[http://dx.doi.org/10.1038/nrrheum.2016.200] [PMID: 27974851]
[29]
Wigerblad G, Bas DB, Fernades-Cerqueira C, et al. Autoantibodies to citrullinated proteins induce joint pain independent of inflammation via a chemokine-dependent mechanism. Ann Rheum Dis 2016; 75(4): 730-8.
[http://dx.doi.org/10.1136/annrheumdis-2015-208094] [PMID: 26613766]
[http://dx.doi.org/10.1136/annrheumdis-2015-208094] [PMID: 26613766]
[30]
Steffen U, Schett G, Bozec A. How autoantibodies regulate osteoclast induced bone loss in rheumatoid arthritis. Front Immunol 2019; 10: 1483.
[http://dx.doi.org/10.3389/fimmu.2019.01483] [PMID: 31333647]
[http://dx.doi.org/10.3389/fimmu.2019.01483] [PMID: 31333647]
[31]
Sudoł-Szopińska I, Kontny E, Maśliński W, et al. The pathogenesis of rheumatoid arthritis in radiological studies. Part I: Formation of inflammatory infiltrates within the synovial membrane. J Ultrason 2012; 12(49): 202-13.
[http://dx.doi.org/10.15557/JoU.2012.0007] [PMID: 26673660]
[http://dx.doi.org/10.15557/JoU.2012.0007] [PMID: 26673660]
[32]
Veale DJ, Orr C, Fearon U. Cellular and molecular perspectives in rheumatoid arthritis. Semin Immunopathol 2017; 39(4): 343-54.
[http://dx.doi.org/10.1007/s00281-017-0633-1] [PMID: 28508153]
[http://dx.doi.org/10.1007/s00281-017-0633-1] [PMID: 28508153]
[33]
L. Ferreira V, H.L. Borba H, de F. Bonetti A, et al. Cytokines and Interferons: Types and Functions.Autoantibodies and Cytokines. IntechOpen 2019.
[34]
Catalan-Dibene J, McIntyre LL, Zlotnik A. Interleukin 30 to Interleukin 40. J Interferon Cytokine Res 2018; 38(10): 423-39.
[http://dx.doi.org/10.1089/jir.2018.0089] [PMID: 30328794]
[http://dx.doi.org/10.1089/jir.2018.0089] [PMID: 30328794]
[35]
Stenken JA, Poschenrieder AJ. Bioanalytical chemistry of cytokines--a review. Anal Chim Acta 2015; 853: 95-115.
[http://dx.doi.org/10.1016/j.aca.2014.10.009] [PMID: 25467452]
[http://dx.doi.org/10.1016/j.aca.2014.10.009] [PMID: 25467452]
[36]
Floege J, Lüscher B, Müller-Newen G. Cytokines and inflammation. Eur J Cell Biol 2012; 91(6-7): 427.
[http://dx.doi.org/10.1016/j.ejcb.2012.01.003] [PMID: 22365147]
[http://dx.doi.org/10.1016/j.ejcb.2012.01.003] [PMID: 22365147]
[37]
Rea IM, Gibson DS, McGilligan V, McNerlan SE, Alexander HD, Ross OA. Age and age-related diseases: Role of inflammation triggers and cytokines. Front Immunol 2018; 9: 586.
[http://dx.doi.org/10.3389/fimmu.2018.00586] [PMID: 29686666]
[http://dx.doi.org/10.3389/fimmu.2018.00586] [PMID: 29686666]
[38]
Farrugia M, Baron B. The role of TNF-α in rheumatoid arthritis: a focus on regulatory T cells. J Clin Transl Res 2016; 2(3): 84-90.
[http://dx.doi.org/10.18053/jctres.02.201603.005] [PMID: 30873466]
[http://dx.doi.org/10.18053/jctres.02.201603.005] [PMID: 30873466]
[39]
Schett G, Dayer JM, Manger B. Interleukin-1 function and role in rheumatic disease. Nat Rev Rheumatol 2016; 12(1): 14-24.
[http://dx.doi.org/10.1038/nrrheum.2016.166] [PMID: 26656658]
[http://dx.doi.org/10.1038/nrrheum.2016.166] [PMID: 26656658]
[40]
Kaneko N, Kurata M, Yamamoto T, et al. The role of interleukin-1 in general pathology. Inflamm Regen 2019; 39: 12.
[http://dx.doi.org/10.1186/s41232-019-0101-5]
[http://dx.doi.org/10.1186/s41232-019-0101-5]
[41]
Favalli EG. Understanding the role of interleukin-6 ( il-6 ) in the joint and beyond : a comprehensive review of il-6 inhibition for the management of rheumatoid arthritis. Rheumatol Ther 2020; 7(3): 473-516.
[42]
Rose-John S. IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6. Int J Biol Sci 2012; 8(9): 1237-47.
[http://dx.doi.org/10.7150/ijbs.4989] [PMID: 23136552]
[http://dx.doi.org/10.7150/ijbs.4989] [PMID: 23136552]
[43]
Churchman SM, El-Jawhari JJ, Burska AN, et al. Modulation of peripheral T-cell function by interleukin-7 in rheumatoid arthritis. Arthritis Res Ther 2014; 16(6): 511.
[44]
Lundström W, Fewkes NM, Mackall CL. IL-7 in human health and disease. Semin Immunol 2012; 24(3): 218-24.
[http://dx.doi.org/10.1016/j.smim.2012.02.005] [PMID: 22410365]
[http://dx.doi.org/10.1016/j.smim.2012.02.005] [PMID: 22410365]
[45]
Kuwabara T, Ishikawa F, Kondo M, Kakiuchi T. The role of il-17 and related cytokines in inflammatory autoimmune diseases. Mediators Inflamm 2017; 2017: 3908061.
[http://dx.doi.org/10.1155/2017/3908061] [PMID: 28316374]
[http://dx.doi.org/10.1155/2017/3908061] [PMID: 28316374]
[46]
Lubberts E. The IL-23-IL-17 axis in inflammatory arthritis. Nat Rev Rheumatol 2015; 11(7): 415-29.
[http://dx.doi.org/10.1038/nrrheum.2015.53] [PMID: 25907700]
[http://dx.doi.org/10.1038/nrrheum.2015.53] [PMID: 25907700]
[47]
Yago T, Nanke Y, Kawamoto M, Kobashigawa T, Yamanaka H, Kotake S. IL-35 inhibits human osteoclastogenesis from monocytes induced by receptor-activator of NF-κB ligand. Cent Eur J Immunol 2018; 43(2): 148-54.
[http://dx.doi.org/10.5114/ceji.2018.77384] [PMID: 30135626]
[http://dx.doi.org/10.5114/ceji.2018.77384] [PMID: 30135626]
[48]
Li Y, Yao L, Liu S, et al. Correlation between serum IL-35 Levels and bone loss in postmenopausal women with rheumatoid arthritis. Mediators Inflamm 2019; 20199139145
[http://dx.doi.org/10.1155/2019/9139145] [PMID: 31534439]
[http://dx.doi.org/10.1155/2019/9139145] [PMID: 31534439]
[49]
Radner H, Aletaha D. Anti-TNF Therapie in der Rheumatoiden Arthritis – ein Überblick. Wien Med Wochenschr 2015; 165: 3-9.
[http://dx.doi.org/10.1007/s10354-015-0344-y] [PMID: 25651945]
[http://dx.doi.org/10.1007/s10354-015-0344-y] [PMID: 25651945]
[50]
van Schouwenburg PA, Rispens T, Wolbink GJ. Immunogenicity of anti-TNF biologic therapies for rheumatoid arthritis. Nat Rev Rheumatol 2013; 9(3): 164-72.
[http://dx.doi.org/10.1038/nrrheum.2013.4] [PMID: 23399692]
[http://dx.doi.org/10.1038/nrrheum.2013.4] [PMID: 23399692]
[51]
Ma X, Xu S. MA X. TNF inhibitor therapy for rheumatoid arthritis. Biomed Rep 2013; 1(2): 177-84.
[http://dx.doi.org/10.3892/br.2012.42] [PMID: 24648915]
[http://dx.doi.org/10.3892/br.2012.42] [PMID: 24648915]
[52]
Chaabo K, Kirkham B. Rheumatoid Arthritis - Anti-TNF. Int Immunopharmacol 2015; 27(2): 180-4.
[http://dx.doi.org/10.1016/j.intimp.2015.04.051] [PMID: 25962818]
[http://dx.doi.org/10.1016/j.intimp.2015.04.051] [PMID: 25962818]
[53]
Bonovas S, Minozzi S, Lytras T, et al. Risk of malignancies using anti-TNF agents in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: a systematic review and meta-analysis. Expert Opin Drug Saf 2016; 15(sup1): 35-54.
[http://dx.doi.org/10.1080/14740338.2016.1238458] [PMID: 27924644]
[http://dx.doi.org/10.1080/14740338.2016.1238458] [PMID: 27924644]
[54]
Markus R, McBride HJ, Ramchandani M, et al. A review of the totality of evidence supporting the development of the first adalimumab biosimilar abp 501. Adv Ther 2019; 36(8): 1833-50.
[http://dx.doi.org/10.1007/s12325-019-00979-6] [PMID: 31183781]
[http://dx.doi.org/10.1007/s12325-019-00979-6] [PMID: 31183781]
[55]
Palomo J, Dietrich D, Martin P, Palmer G, Gabay C. The interleukin (IL)-1 cytokine family--Balance between agonists and antagonists in inflammatory diseases. Cytokine 2015; 76(1): 25-37.
[http://dx.doi.org/10.1016/j.cyto.2015.06.017] [PMID: 26185894]
[http://dx.doi.org/10.1016/j.cyto.2015.06.017] [PMID: 26185894]
[56]
Dayer J-M, Oliviero F, Punzi L. A Brief History of IL-1 and IL-1 Ra in Rheumatology. Front Pharmacol 2017; 8: 293.
[http://dx.doi.org/10.3389/fphar.2017.00293] [PMID: 28588495]
[http://dx.doi.org/10.3389/fphar.2017.00293] [PMID: 28588495]
[57]
Kaneko N, Kurata M, Yamamoto T, Morikawa S, Masumoto J. The role of interleukin-1 in general pathology. Inflamm Regen 2019; 39: 12.
[http://dx.doi.org/10.1186/s41232-019-0101-5] [PMID: 31182982]
[http://dx.doi.org/10.1186/s41232-019-0101-5] [PMID: 31182982]
[58]
The role of interleukin 1 in the pathogenesis of rheumatoid arthritis https://pubmed.ncbi.nlm.nih.gov/3326690/
[59]
Dayer JM. The pivotal role of interleukin-1 in the clinical manifestations of rheumatoid arthritis. Rheumatology (Oxford) 42(Suppl 2): ii3-10.
[http://dx.doi.org/10.1093/rheumatology/keg326]
[http://dx.doi.org/10.1093/rheumatology/keg326]
[60]
Burger D, Dayer JM, Palmer G, Gabay C. Is IL-1 a good therapeutic target in the treatment of arthritis? Best Pract Res Clin Rheumatol 2006; 20(5): 879-96.
[http://dx.doi.org/10.1016/j.berh.2006.06.004] [PMID: 16980212]
[http://dx.doi.org/10.1016/j.berh.2006.06.004] [PMID: 16980212]
[61]
Dinarello CA. The IL-1 family of cytokines and receptors in rheumatic diseases. Nat Rev Rheumatol 2019; 15(10): 612-32.
[http://dx.doi.org/10.1038/s41584-019-0277-8] [PMID: 31515542]
[http://dx.doi.org/10.1038/s41584-019-0277-8] [PMID: 31515542]
[62]
Furst DE. Anakinra: review of recombinant human interleukin-I receptor antagonist in the treatment of rheumatoid arthritis. Clin Ther 2004; 26(12): 1960-75.
[http://dx.doi.org/10.1016/j.clinthera.2004.12.019] [PMID: 15823761]
[http://dx.doi.org/10.1016/j.clinthera.2004.12.019] [PMID: 15823761]
[63]
Rondeau JM, Ramage P, Zurini M, Gram H. The molecular mode of action and species specificity of canakinumab, a human monoclonal antibody neutralizing IL-1β. MAbs 2015; 7(6): 1151-60.
[http://dx.doi.org/10.1080/19420862.2015.1081323] [PMID: 26284424]
[http://dx.doi.org/10.1080/19420862.2015.1081323] [PMID: 26284424]
[64]
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): 2196-204.
[http://dx.doi.org/10.1002/1529-0131(199812)41:12<2196::AID-ART15>3.0.CO;2-2] [PMID: 9870876]
[http://dx.doi.org/10.1002/1529-0131(199812)41:12<2196::AID-ART15>3.0.CO;2-2] [PMID: 9870876]
[65]
Nuki G, Bresnihan B, Bear MB, McCabe D. European Group Of Clinical Investigators. Long-term safety and maintenance of clinical improvement following treatment with anakinra (recombinant human interleukin-1 receptor antagonist) in patients with rheumatoid arthritis: extension phase of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2002; 46(11): 2838-46.
[http://dx.doi.org/10.1002/art.10578] [PMID: 12428223]
[http://dx.doi.org/10.1002/art.10578] [PMID: 12428223]
[66]
Cohen SB, Woolley JM, Chan W. Anakinra 960180 Study Group. Interleukin 1 receptor antagonist anakinra improves functional status in patients with rheumatoid arthritis. J Rheumatol 2003; 30(2): 225-31.
[PMID: 12563672]
[PMID: 12563672]
[67]
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, placebo-controlled trial. Arthritis Rheum 2002; 46(3): 614-24.
[http://dx.doi.org/10.1002/art.10141] [PMID: 11920396]
[http://dx.doi.org/10.1002/art.10141] [PMID: 11920396]
[68]
Cohen SB. The use of anakinra, an interleukin-1 receptor antagonist, in the treatment of rheumatoid arthritis. Rheum Dis Clin North Am 2004; 30(2): 365-80.
[http://dx.doi.org/10.1016/j.rdc.2004.01.005] [PMID: 15172046]
[http://dx.doi.org/10.1016/j.rdc.2004.01.005] [PMID: 15172046]
[69]
Fleischmann RM, Schechtman J, Bennett R, et al. Anakinra, a recombinant human interleukin-1 receptor antagonist (r-metHuIL-1ra), in patients with rheumatoid arthritis: A large, international, multicenter, placebo-controlled trial. Arthritis Rheum 2003; 48(4): 927-34.
[http://dx.doi.org/10.1002/art.10870] [PMID: 12687534]
[http://dx.doi.org/10.1002/art.10870] [PMID: 12687534]
[70]
Fleischmann RM, Tesser J, Schiff MH, et al. Safety of extended treatment with anakinra in patients with rheumatoid arthritis. Ann Rheum Dis 2006; 65(8): 1006-12.
[http://dx.doi.org/10.1136/ard.2005.048371] [PMID: 16396977]
[http://dx.doi.org/10.1136/ard.2005.048371] [PMID: 16396977]
[71]
Cardiel MH, Tak PP, Bensen W, et al. A phase 2 randomized, double-blind study of AMG 108, a fully human monoclonal antibody to IL-1R, in patients with rheumatoid arthritis. Arthritis Res Ther 2010; 12(5): R192.
[72]
Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta 2011; 1813(5): 878-88.
[http://dx.doi.org/10.1016/j.bbamcr.2011.01.034] [PMID: 21296109]
[http://dx.doi.org/10.1016/j.bbamcr.2011.01.034] [PMID: 21296109]
[73]
Yao X, Huang J, Zhong H, et al. Targeting interleukin-6 in inflammatory autoimmune diseases and cancers. Pharmacol Ther 2014; 141(2): 125-39.
[http://dx.doi.org/10.1016/j.pharmthera.2013.09.004] [PMID: 24076269]
[http://dx.doi.org/10.1016/j.pharmthera.2013.09.004] [PMID: 24076269]
[74]
Kim GW, Lee NR, Pi RH, et al. IL-6 inhibitors for treatment of rheumatoid arthritis: past, present, and future. Arch Pharm Res 2015; 38(5): 575-84.
[http://dx.doi.org/10.1007/s12272-015-0569-8] [PMID: 25648633]
[http://dx.doi.org/10.1007/s12272-015-0569-8] [PMID: 25648633]
[75]
Kaneshiro K, Sakai Y, Suzuki K, et al. Interleukin-6 and tumour necrosis factor-α cooperatively promote cell cycle regulators and proliferate rheumatoid arthritis fibroblast-like synovial cells. Scand J Rheumatol 2019; 48(5): 353-61.
[http://dx.doi.org/10.1080/03009742.2019.1602164] [PMID: 31631790]
[http://dx.doi.org/10.1080/03009742.2019.1602164] [PMID: 31631790]
[76]
Mihara M, Hashizume M, Yoshida H, Suzuki M, Shiina M. IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci (Lond) 2012; 122(4): 143-59.
[http://dx.doi.org/10.1042/CS20110340] [PMID: 22029668]
[http://dx.doi.org/10.1042/CS20110340] [PMID: 22029668]
[77]
Mitchell E, Jones G. Subcutaneous tocilizumab for the treatment of rheumatoid arthritis. Expert Rev Clin Immunol 2016; 12(2): 103-14.
[http://dx.doi.org/10.1586/1744666X.2016.1127159] [PMID: 26629984]
[http://dx.doi.org/10.1586/1744666X.2016.1127159] [PMID: 26629984]
[78]
Sheppard M, Laskou F, Stapleton PP, Hadavi S, Dasgupta B. Tocilizumab (Actemra). Hum Vaccin Immunother 2017; 13(9): 1972-88.
[http://dx.doi.org/10.1080/21645515.2017.1316909] [PMID: 28841363]
[http://dx.doi.org/10.1080/21645515.2017.1316909] [PMID: 28841363]
[79]
Nishimoto N, Hashimoto J, Miyasaka N, et al. Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an x ray reader-blinded randomised controlled trial of tocilizumab. Ann Rheum Dis 2007; 66(9): 1162-7.
[http://dx.doi.org/10.1136/ard.2006.068064] [PMID: 17485422]
[http://dx.doi.org/10.1136/ard.2006.068064] [PMID: 17485422]
[80]
Tanaka Y, Wada K, Takahashi Y, et al. Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: results of a randomized, placebo-controlled phase III trial in Japan. Arthritis Res Ther 2019; 21(1): 79-9.
[http://dx.doi.org/10.1186/s13075-019-1856-4] [PMID: 30894208]
[http://dx.doi.org/10.1186/s13075-019-1856-4] [PMID: 30894208]
[81]
Akashi K, Kondo M, Weissman IL. Role of interleukin-7 in T-cell development from hematopoietic stem cells. Immunol Rev 1998; 165: 13-28.
[http://dx.doi.org/10.1111/j.1600-065X.1998.tb01226.x] [PMID: 9850848]
[http://dx.doi.org/10.1111/j.1600-065X.1998.tb01226.x] [PMID: 9850848]
[82]
Mackall CL, Fry TJ, Gress RE. Harnessing the biology of IL-7 for therapeutic application. Nat Rev Immunol 2011; 11(5): 330-42.
[http://dx.doi.org/10.1038/nri2970] [PMID: 21508983]
[http://dx.doi.org/10.1038/nri2970] [PMID: 21508983]
[83]
Barata JT, Durum SK, Seddon B. Flip the coin: IL-7 and IL-7R in health and disease. Nat Immunol 2019; 20(12): 1584-93.
[http://dx.doi.org/10.1038/s41590-019-0479-x] [PMID: 31745336]
[http://dx.doi.org/10.1038/s41590-019-0479-x] [PMID: 31745336]
[84]
Churchman SM, Ponchel F. Interleukin-7 in rheumatoid arthritis. Rheumatology (Oxford) 2008; 47(6): 753-9.
[http://dx.doi.org/10.1093/rheumatology/ken053] [PMID: 18356170]
[http://dx.doi.org/10.1093/rheumatology/ken053] [PMID: 18356170]
[85]
Cai L, Xu H, Zhang H, Zhang L, Wang G, Nie H. Blockade of IL-7Rα alleviates collagen-induced arthritis via inhibiting Th1 cell differentiation and CD4+ T cell migration. Mol Immunol 2016; 79: 83-91.
[http://dx.doi.org/10.1016/j.molimm.2016.09.017] [PMID: 27736699]
[http://dx.doi.org/10.1016/j.molimm.2016.09.017] [PMID: 27736699]
[86]
Dooms H. Interleukin-7: Fuel for the autoimmune attack. J Autoimmun 2013; 45: 40-8.
[http://dx.doi.org/10.1016/j.jaut.2013.06.007] [PMID: 23831438]
[http://dx.doi.org/10.1016/j.jaut.2013.06.007] [PMID: 23831438]
[87]
Cutolo M. The kinase inhibitor tofacitinib in patients with rheumatoid arthritis: latest findings and clinical potential. Ther Adv Musculoskelet Dis 2013; 5(1): 3-11.
[http://dx.doi.org/10.1177/1759720X12470753] [PMID: 23515130]
[http://dx.doi.org/10.1177/1759720X12470753] [PMID: 23515130]
[88]
Song X, Qian Y. IL-17 family cytokines mediated signaling in the pathogenesis of inflammatory diseases. Cell Signal 2013; 25(12): 2335-47.
[http://dx.doi.org/10.1016/j.cellsig.2013.07.021] [PMID: 23917206]
[http://dx.doi.org/10.1016/j.cellsig.2013.07.021] [PMID: 23917206]
[89]
Monin L, Gaffen SL. Interleukin 17 family cytokines: Signaling mechanisms, biological activities, and therapeutic implications. Cold Spring Harb Perspect Biol 2018; 10(4): a028522.
[90]
McGeachy MJ, Cua DJ, Gaffen SL. The IL-17 Family of Cytokines in Health and Disease. Immunity 2019; 50(4): 892-906.
[http://dx.doi.org/10.1016/j.immuni.2019.03.021] [PMID: 30995505]
[http://dx.doi.org/10.1016/j.immuni.2019.03.021] [PMID: 30995505]
[91]
Robert M, Miossec P. IL-17 in rheumatoid arthritis and precision medicine: From synovitis expression to circulating bioactive levels. Frontiers in Medicine
[92]
Kunwar S, Dahal K, Sharma S. Anti-IL-17 therapy in treatment of rheumatoid arthritis: a systematic literature review and meta-analysis of randomized controlled trials. Rheumatol Int 2016; 36(8): 1065-75.
[http://dx.doi.org/10.1007/s00296-016-3480-9] [PMID: 27105880]
[http://dx.doi.org/10.1007/s00296-016-3480-9] [PMID: 27105880]
[93]
Zintzaras E, Dahabreh IJ, Giannouli S, Voulgarelis M, Moutsopoulos HM. Infliximab and methotrexate in the treatment of rheumatoid arthritis: a systematic review and meta-analysis of dosage regimens. Clin Ther 2008; 30(11): 1939-55.
[http://dx.doi.org/10.1016/j.clinthera.2008.11.007] [PMID: 19108784]
[http://dx.doi.org/10.1016/j.clinthera.2008.11.007] [PMID: 19108784]
[94]
Hueber W, Patel DD, Dryja T, et al. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med 2010; 2(52): 52ra72.
[95]
Martin DA, Churchill M, Flores-Suarez LF, et al. A phase Ib multiple ascending dose study evaluating safety, pharmacokinetics, and early clinical response of brodalumab, a human anti-IL-17R antibody, in methotrexate-resistant rheumatoid arthritis. Arthritis Res Ther 2013; 15(5): R164.
[96]
Genovese MC, Van den Bosch F, Roberson SA, et al. LY2439821, a humanized anti-interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: A phase I randomized, double-blind, placebo-controlled, proof-of-concept study. Arthritis Rheum 2010; 62(4): 929-39.
[http://dx.doi.org/10.1002/art.27334] [PMID: 20131262]
[http://dx.doi.org/10.1002/art.27334] [PMID: 20131262]
[97]
Guan SY, Leng RX, Khan MI, et al. Interleukin-35: a potential therapeutic agent for autoimmune diseases. Inflammation 2017; 40(1): 303-10.
[http://dx.doi.org/10.1007/s10753-016-0453-9] [PMID: 27696334]
[http://dx.doi.org/10.1007/s10753-016-0453-9] [PMID: 27696334]
[98]
Li Y, Yao L, Liu S, et al. Elevated serum IL-35 levels in rheumatoid arthritis are associated with disease activity. J Investig Med 2019; 67(3): 707-10.
[http://dx.doi.org/10.1136/jim-2018-000814] [PMID: 30659089]
[http://dx.doi.org/10.1136/jim-2018-000814] [PMID: 30659089]
[99]
Ye L, Wen Z, Li Y, et al. Interleukin-10 attenuation of collagen-induced arthritis is associated with suppression of interleukin-17 and retinoid-related orphan receptor γt production in macrophages and repression of classically activated macrophages. Arthritis Res Ther 2014; 16(2): R96.
[http://dx.doi.org/10.1186/ar4544] [PMID: 24742125]
[http://dx.doi.org/10.1186/ar4544] [PMID: 24742125]
[100]
Su LC, Liu XY, Huang AF, Xu WD. Emerging role of IL-35 in inflammatory autoimmune diseases. Autoimmun Rev 2018; 17(7): 665-73.
[http://dx.doi.org/10.1016/j.autrev.2018.01.017] [PMID: 29729445]
[http://dx.doi.org/10.1016/j.autrev.2018.01.017] [PMID: 29729445]
[101]
Bello RO, Chin VK, Abd Rachman Isnadi MF, et al. The role, involvement and function(S) of interleukin-35 and interleukin-37 in disease pathogenesis. International Journal of Molecular Sciences 2018; 19(4): 1149.
[102]
Ning X, Jian Z, Wang W. Low serum levels of interleukin 35 in patients with rheumatoid arthritis. Tohoku J Exp Med 2015; 237(2): 77-82.
[http://dx.doi.org/10.1620/tjem.237.77] [PMID: 26370008]
[http://dx.doi.org/10.1620/tjem.237.77] [PMID: 26370008]
Article Metrics
![Wayfinder Image](/images/wayfinder.jpg)