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Erschienen in: Modern Rheumatology 6/2009

01.12.2009 | Original Article

Infliximab treatment reduces the serum levels of interleukin-23 in patients with rheumatoid arthritis

verfasst von: Yasunori Kageyama, Hayato Kobayashi, Norihiko Kato

Erschienen in: Modern Rheumatology | Ausgabe 6/2009

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Abstract

In this study, we investigated the effect of the antitumor necrosis factor alpha (anti-TNF-α) antibody, infliximab, combined with methotrexate (MTX) and MTX alone on the serum levels of interleukin (IL)-23 and IL-17 in rheumatoid arthritis (RA) patients. Infliximab combined with MTX was administered to 26 patients with RA (infliximab group), and MTX alone was given to 20 patients with RA (MTX group). We evaluated clinical and laboratory parameters, including the Disease Activity Scores of 28 joints (DAS28) and serum levels of IL-23 and IL-17 at baseline and at 14 and 30 weeks after the initial treatment with these drugs. Single regression analysis was performed between the levels of serum IL-23 and other clinical and laboratory parameters at baseline before the initial treatment with infliximab or MTX. A significant reduction of DAS28 scores was observed in both the infliximab and the MTX group at 14 and 30 weeks after the initial treatment. A significant decrease in serum levels of IL-23 was observed in the infliximab group but not in the MTX group at 14 and 30 weeks after the initial treatment. Serum IL-17 levels did not show a significant change during the follow-up period. At baseline, before the initial treatment with infliximab or MTX, serum IL-23 levels showed a significant correlation with DAS28 and the number of swollen joints. This study indicated that the reduction of serum IL-23 levels in RA patients was a novel action of infliximab.
Literatur
1.
Zurück zum Zitat Arend WP, Dayer J-M. Inhibition of the production and effects of interleukin-1 and tumor necrosis factor alpha in rheumatoid arthritis. Arthritis Rheum. 1995;38:151–60.CrossRefPubMed Arend WP, Dayer J-M. Inhibition of the production and effects of interleukin-1 and tumor necrosis factor alpha in rheumatoid arthritis. Arthritis Rheum. 1995;38:151–60.CrossRefPubMed
2.
Zurück zum Zitat Maini RN, Taylor PC. Anti-cytokine therapy for rheumatoid arthritis. Ann Rev Med. 2000;51:207–29.CrossRefPubMed Maini RN, Taylor PC. Anti-cytokine therapy for rheumatoid arthritis. Ann Rev Med. 2000;51:207–29.CrossRefPubMed
3.
Zurück zum Zitat Ingegnoli F, Fantini F, Favalli EG, Soldi A, Griffini S, Galbiati V, et al. Inflammatory and prothrombotic biomarkers in patients with rheumatoid arthritis: effects of tumor necrosis factor-alpha blockade. J Autoimmun. 2008;31:175–9.CrossRefPubMed Ingegnoli F, Fantini F, Favalli EG, Soldi A, Griffini S, Galbiati V, et al. Inflammatory and prothrombotic biomarkers in patients with rheumatoid arthritis: effects of tumor necrosis factor-alpha blockade. J Autoimmun. 2008;31:175–9.CrossRefPubMed
4.
Zurück zum Zitat Pittoni V, Bombardieri M, Spinelli FR, Scrivo R, Alessandri C, Conti F, et al. Anti-tumor necrosis factor (TNF) alpha treatment of rheumatoid arthritis (infliximab) selectively down regulates the production of interleukin (IL) 18 but not of IL12 and IL13. Ann Rheum Dis. 2002;61:723–5.CrossRefPubMed Pittoni V, Bombardieri M, Spinelli FR, Scrivo R, Alessandri C, Conti F, et al. Anti-tumor necrosis factor (TNF) alpha treatment of rheumatoid arthritis (infliximab) selectively down regulates the production of interleukin (IL) 18 but not of IL12 and IL13. Ann Rheum Dis. 2002;61:723–5.CrossRefPubMed
5.
Zurück zum Zitat Klimiuk PA, Sierakowski S, Domyslawska I, Chwiecko J. Effect of repeated infliximab therapy on serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with rheumatoid arthritis. J Rheumatol. 2004;31:238–42.PubMed Klimiuk PA, Sierakowski S, Domyslawska I, Chwiecko J. Effect of repeated infliximab therapy on serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with rheumatoid arthritis. J Rheumatol. 2004;31:238–42.PubMed
6.
Zurück zum Zitat Levälampi T, Honkanen V, Lahdenne P, Nieminen R, Hakala M, Moilanen E. Effects of infliximab on cytokines, myeloperoxidase, and soluble adhesion molecules in patients with juvenile idiopathic arthritis. Scand J Rheumatol. 2007;36:189–93.CrossRefPubMed Levälampi T, Honkanen V, Lahdenne P, Nieminen R, Hakala M, Moilanen E. Effects of infliximab on cytokines, myeloperoxidase, and soluble adhesion molecules in patients with juvenile idiopathic arthritis. Scand J Rheumatol. 2007;36:189–93.CrossRefPubMed
7.
Zurück zum Zitat Haworth C, Brennan FM, Chantry D, Turner M, Maini RN, Feldmann M. Expression of granulocyte-macrophage colony-stimulating factor in rheumatoid arthritis: regulation by tumor necrosis factor-alpha. Eur J Immunol. 1991;21:2575–9.CrossRefPubMed Haworth C, Brennan FM, Chantry D, Turner M, Maini RN, Feldmann M. Expression of granulocyte-macrophage colony-stimulating factor in rheumatoid arthritis: regulation by tumor necrosis factor-alpha. Eur J Immunol. 1991;21:2575–9.CrossRefPubMed
8.
Zurück zum Zitat Kageyama Y, Takahashi M, Torikai E, Suzuki M, Ichikawa T, Nagafusa T, et al. Treatment with anti-TNF-alpha antibody infliximab reduces serum IL-15 levels in patients with rheumatoid arthritis. Clin Rheumatol. 2007;26:505–9.CrossRefPubMed Kageyama Y, Takahashi M, Torikai E, Suzuki M, Ichikawa T, Nagafusa T, et al. Treatment with anti-TNF-alpha antibody infliximab reduces serum IL-15 levels in patients with rheumatoid arthritis. Clin Rheumatol. 2007;26:505–9.CrossRefPubMed
9.
Zurück zum Zitat Torikai E, Kageyama Y, Suzuki M, Ichikawa T, Nagano A. The effect of infliximab on chemokines in patients with rheumatoid arthritis. Clin Rheumatol. 2007;26:1088–93.CrossRefPubMed Torikai E, Kageyama Y, Suzuki M, Ichikawa T, Nagano A. The effect of infliximab on chemokines in patients with rheumatoid arthritis. Clin Rheumatol. 2007;26:1088–93.CrossRefPubMed
10.
Zurück zum Zitat Kikly K, Liu L, Na S, Sedgwick JD. The IL-23/Th(17) axis: therapeutic targets for autoimmune inflammation. Curr Opin Immunol. 2006;18:670–5.CrossRefPubMed Kikly K, Liu L, Na S, Sedgwick JD. The IL-23/Th(17) axis: therapeutic targets for autoimmune inflammation. Curr Opin Immunol. 2006;18:670–5.CrossRefPubMed
11.
Zurück zum Zitat Brentano F, Ospelt C, Stanczyk J, Gay RE, Gay S, Kyburz D. Abundant expression of the interleukin (IL)23 subunit p19, but low levels of bioactive IL23 in the rheumatoid synovium: differential expression and Toll-like receptor-(TLR) dependent regulation of the IL23 subunits, p19 and p40, in rheumatoid arthritis. Ann Rheum Dis. 2009;68:143–50.CrossRefPubMed Brentano F, Ospelt C, Stanczyk J, Gay RE, Gay S, Kyburz D. Abundant expression of the interleukin (IL)23 subunit p19, but low levels of bioactive IL23 in the rheumatoid synovium: differential expression and Toll-like receptor-(TLR) dependent regulation of the IL23 subunits, p19 and p40, in rheumatoid arthritis. Ann Rheum Dis. 2009;68:143–50.CrossRefPubMed
12.
Zurück zum Zitat Spanakis E, Sidiropoulos P, Papadakis J, Ganotakis E, Katsikas G, Karvounaris S, et al. Modest but sustained increase of serum high density lipoprotein cholesterol levels in patients with inflammatory arthritides treated with infliximab. J Rheumatol. 2006;33:2440–6.PubMed Spanakis E, Sidiropoulos P, Papadakis J, Ganotakis E, Katsikas G, Karvounaris S, et al. Modest but sustained increase of serum high density lipoprotein cholesterol levels in patients with inflammatory arthritides treated with infliximab. J Rheumatol. 2006;33:2440–6.PubMed
13.
Zurück zum Zitat Kim HR, Kim HS, Park MK, Cho ML, Lee SH, Kim HY. The clinical role of IL-23p19 in patients with rheumatoid arthritis. Scand J Rheumatol. 2007;36:259–64.CrossRefPubMed Kim HR, Kim HS, Park MK, Cho ML, Lee SH, Kim HY. The clinical role of IL-23p19 in patients with rheumatoid arthritis. Scand J Rheumatol. 2007;36:259–64.CrossRefPubMed
14.
Zurück zum Zitat Mitoma H, Horiuchi T, Hatta N, Tsukamoto H, Harashima S, Kikuchi Y, et al. Infliximab induces potent anti-inflammatory responses by outside-to-inside signals through transmembrane TNF-alpha. Gastroenterology. 2005;128:376–92.CrossRefPubMed Mitoma H, Horiuchi T, Hatta N, Tsukamoto H, Harashima S, Kikuchi Y, et al. Infliximab induces potent anti-inflammatory responses by outside-to-inside signals through transmembrane TNF-alpha. Gastroenterology. 2005;128:376–92.CrossRefPubMed
15.
Zurück zum Zitat Kinne RW, Brauer R, Stuhlmuller B, Palombo-Kinne E, Burmester GR. Macrophages in rheumatoid arthritis. Arthritis Res. 2000;2:189–202.CrossRefPubMed Kinne RW, Brauer R, Stuhlmuller B, Palombo-Kinne E, Burmester GR. Macrophages in rheumatoid arthritis. Arthritis Res. 2000;2:189–202.CrossRefPubMed
16.
Zurück zum Zitat Murphy CA, Langrish CL, Chen Y, Blumenschein W, McClanahan T, Kastelein RA, et al. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med. 2003;198:1951–7.CrossRefPubMed Murphy CA, Langrish CL, Chen Y, Blumenschein W, McClanahan T, Kastelein RA, et al. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med. 2003;198:1951–7.CrossRefPubMed
17.
Zurück zum Zitat Chen L, Wei XQ, Evans B, Jiang W, Aeschlimann D. IL-23 promotes osteoclast formation by up-regulation of receptor activator of NF-kappa B (RANK) expression in myeloid precursor cells. Eur J Immunol. 2008;38:2845–54.CrossRefPubMed Chen L, Wei XQ, Evans B, Jiang W, Aeschlimann D. IL-23 promotes osteoclast formation by up-regulation of receptor activator of NF-kappa B (RANK) expression in myeloid precursor cells. Eur J Immunol. 2008;38:2845–54.CrossRefPubMed
18.
Zurück zum Zitat Atkins GJ, Haynes DR, Geary SM, Loric M, Crotti TN, Findlay DM. Coordinated cytokine expression by stromal and hematopoietic cells during human osteoclast formation. Bone. 2000;26:653–6.CrossRefPubMed Atkins GJ, Haynes DR, Geary SM, Loric M, Crotti TN, Findlay DM. Coordinated cytokine expression by stromal and hematopoietic cells during human osteoclast formation. Bone. 2000;26:653–6.CrossRefPubMed
19.
Zurück zum Zitat Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, et al. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest. 1999;103:1345–52.CrossRefPubMed Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, et al. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest. 1999;103:1345–52.CrossRefPubMed
20.
Zurück zum Zitat Kolls JK, Linden A. Interleukin-17 family members and inflammation. Immunity. 2004;21:467–76.CrossRefPubMed Kolls JK, Linden A. Interleukin-17 family members and inflammation. Immunity. 2004;21:467–76.CrossRefPubMed
21.
Zurück zum Zitat Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature. 2003;421:744–8.CrossRefPubMed Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature. 2003;421:744–8.CrossRefPubMed
22.
Zurück zum Zitat Listing J, Strangfeld A, Kekow J, Schneider M, Kapelle A, Wassenberg S, et al. Does tumor necrosis factor alpha inhibition promote or prevent heart failure in patients with rheumatoid arthritis? Arthritis Rheum. 2008;58:667–77.CrossRefPubMed Listing J, Strangfeld A, Kekow J, Schneider M, Kapelle A, Wassenberg S, et al. Does tumor necrosis factor alpha inhibition promote or prevent heart failure in patients with rheumatoid arthritis? Arthritis Rheum. 2008;58:667–77.CrossRefPubMed
23.
Zurück zum Zitat Kageyama Y, Ichikawa T, Nagafusa T, Torikai E, Shimazu M, Nagano A. Etanercept reduces the serum levels of interleukin-23 and macrophage inflammatory protein-3 alpha in patients with rheumatoid arthritis. Rheumatol Int. 2008;28:137–43.CrossRef Kageyama Y, Ichikawa T, Nagafusa T, Torikai E, Shimazu M, Nagano A. Etanercept reduces the serum levels of interleukin-23 and macrophage inflammatory protein-3 alpha in patients with rheumatoid arthritis. Rheumatol Int. 2008;28:137–43.CrossRef
24.
Zurück zum Zitat Happel KI, Zheng M, Young E, Quinton LJ, Lockhart E, Ramsay AJ, et al. Cutting edge: roles of Toll-like receptor 4 and IL-23 in IL-17 expression in response to Klebsiella pneumoniae infection. J Immunol. 2003;170:4432–6.PubMed Happel KI, Zheng M, Young E, Quinton LJ, Lockhart E, Ramsay AJ, et al. Cutting edge: roles of Toll-like receptor 4 and IL-23 in IL-17 expression in response to Klebsiella pneumoniae infection. J Immunol. 2003;170:4432–6.PubMed
25.
Zurück zum Zitat Ziolkowska M, Koc A, Luszczykiewicz G, Ksiezopolska-Pietrzak K, Klimczak E, Chwalinska-Sadowska H. High levels of IL-17 in rheumatoid arthritis patients: IL-15 triggers in vitro IL-17 production via cyclosporin A-sensitive mechanism. J Immunol. 2000;164:2832–8.PubMed Ziolkowska M, Koc A, Luszczykiewicz G, Ksiezopolska-Pietrzak K, Klimczak E, Chwalinska-Sadowska H. High levels of IL-17 in rheumatoid arthritis patients: IL-15 triggers in vitro IL-17 production via cyclosporin A-sensitive mechanism. J Immunol. 2000;164:2832–8.PubMed
Metadaten
Titel
Infliximab treatment reduces the serum levels of interleukin-23 in patients with rheumatoid arthritis
verfasst von
Yasunori Kageyama
Hayato Kobayashi
Norihiko Kato
Publikationsdatum
01.12.2009
Verlag
Springer Japan
Erschienen in
Modern Rheumatology / Ausgabe 6/2009
Print ISSN: 1439-7595
Elektronische ISSN: 1439-7609
DOI
https://doi.org/10.1007/s10165-009-0217-6

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