Skip to main content

Advertisement

Log in

The effect of infliximab on chemokines in patients with rheumatoid arthritis

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by infiltration of lymphocytes, macrophages, and plasma cells into synovial membrane. The chemokines family promotes chemotactic activity in various leukocyte cell types. Chemokines thus play an essential role in the pathological formation of RA. The aim of the present study was to evaluate the influence of infliximab on serum levels of various chemokines. Twenty-four RA patients were involved in this study, which took place between March 2003 and February 2006. Infliximab was administered by intravenous infusion at a dosage of 3 mg/kg. All patients underwent general and physical examinations and routine blood and urinary analysis at the baseline, at 14 weeks, and at 30 weeks after the initial treatment. To determine whether serum and synovial fluid from RA also contained significant levels of chemokines compared with osteoarthritis patients (OA), GRO-α, MIP-1α, MIP-1β and regulated on activation normal T cell expressed and secreted (RANTES) levels of serum and synovial fluid were measured by ELISA in 20 RA patients and 20 OA patients. GRO-α, MIP-1β, and RANTES levels were significantly higher in RA compared with normal volunteers, while MIP-1α levels showed no significant differences. The mean GRO-α levels in serum from RA patients treated with infliximab decreased significantly after the initial treatment. The mean RANTES and MIP-1β levels did not change significantly after the treatment. Infliximab treatment significantly lowered the serum GRO-α levels of RA patients. GRO-α is one of the crucial cytokines affected by infliximab treatment. The blocking therapy of RANTES and MIP-1β combined with infliximab treatment may have an additional effect without competition in the TNFα cascade.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Szekanecz Z, Strieter RM, Kunnkel SL, Koch AE (1998) Chemokines in rheumatoid arthritis. Springer Semin Immunopathol 20:115–132

    Article  PubMed  CAS  Google Scholar 

  2. Fujiwara K, Motsukawa A, Ohkawara S, Takagi K, Yoshinaga M (2002) Functional distinction between CXC chemokines, interleukin-8 (IL-8), and grown related oncogene (GRO-α) in neutrophil infiltration. Lab Invest 82:15–23

    PubMed  CAS  Google Scholar 

  3. Seiz M, Dewald B, Gerber N, Baggiolini M (1991) Enhanced production of neutrophil-activating peptide-1/interleukin-8 in rheumatoid arthritis. J Clin Invest 87:463–469

    Google Scholar 

  4. Schroder JM, Gregory H, Young J, Christophers E (1992) J Invest Dermatol 98:241–247

    Article  PubMed  CAS  Google Scholar 

  5. Wen DZ, Rowland A, Derynck R (1989) Expression and secretion of gro/MGSA by stimulated human endothelial cells. EMBO J 8:1761–1766

    PubMed  CAS  Google Scholar 

  6. Schroder JM, Sticherling M, Henneicke HH, Preissner WC, Christophers E (1990) IL-1α or TNF-α stimulate release of three NAP-1/IL-8-related neutrophil chemotactic proteins in human dermal fibroblasts. J Immunol 144:2223–2232

    PubMed  CAS  Google Scholar 

  7. Stoeckle MY (1991) Post-transcriptional regulation of groα,β,γ and IL-8 mRNAs by IL-1β. Nucleic Acids Res 19:917–920

    Article  PubMed  CAS  Google Scholar 

  8. Oppenheum JJ, Zachariae CO, Mukaida N, Matsushima K (1991) Prperties of the novel proinflammatory supergene “intercrine” cytokine family. Annu Rev Immunol 9:617–648

    Google Scholar 

  9. Schall TJ, Bacon K, Toy KJ et al (1990) Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES. Nature 347:669–671

    Article  PubMed  CAS  Google Scholar 

  10. Taub DD, Oppenheim JJ (1994) Chemokines, inflammation and the immune system. Ther Immunol 1:229–246

    PubMed  CAS  Google Scholar 

  11. Kunkel SL, Lukacs N, Kasama T, Strieter RM (1996) The role of chemokines in inflammatory joint disease. J Leukoc Biol 59:6–12

    PubMed  CAS  Google Scholar 

  12. Elliott MJ, Maini RN, Fledmann M, Long-Fox A, Charles P, Katsikis P et al (1993) Treatment of rheumatoid arthritis with cheimeric monoclonal antibodies to tumor necrosis factor α. Arthritis Rheum 36:1681–1690

    Article  PubMed  CAS  Google Scholar 

  13. Moreland LW, Baumgartner SW, Schiff MH, Tindall EA, Fleischmann RM, Weaver AL et al (1997) Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p-75)-Fc fusion protein. N Engl J Med 337:141–147

    Article  PubMed  CAS  Google Scholar 

  14. Haringman JJ, Ludikhuize J, Tak PP (2000) Chemokines in joint disease: the key to inflammation? Ann Rheum Dis 63:1186–1194

    Article  CAS  Google Scholar 

  15. Szekanecz Z, Koch AE (2001) Chemokines and angiogenesis. Curr Opin Rheumatol 13:202–208

    Article  PubMed  CAS  Google Scholar 

  16. Richmond A, Thomas HG (1988) Melanoma growth stimulatory activity: isolation from human melanoma tumors and characterization of tissue distribution. J Cell Biochem 36:185–198

    Article  PubMed  CAS  Google Scholar 

  17. Arnett FC, Edworthy SM, Bloch DA et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324

    Article  PubMed  CAS  Google Scholar 

  18. Van der Heijde DM, van’t Hof MA, van Riel PL, Theunisse LA, Lubberts EW, van Leeuwen MA et al (1990) Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a disease activity score. Ann Rheum Dis 49:916–920

    Article  PubMed  Google Scholar 

  19. Richmond A, Lawson DH, Nixon DW, Stevens JS, Chawla RK (1983) Extraction of a melanoma growth-stimulatory activity from culture medium conditioned by the Hs0294 human melanoma cell line. Cancer Res 43:2106–2112

    PubMed  CAS  Google Scholar 

  20. Ellingsen T, Buus A, Moller BK, Stengaard-Pedersen K (2000) In vitro migration of mononuclear cells towards synovial fluid and plasma from rheumatoid arthritis patients correlates to RANTES synovial fluid levels and to clinical pain parameters. Scand J Rheumatol 29:216–221

    Article  PubMed  CAS  Google Scholar 

  21. Robinson E, Keystone EC, Schall TJ, Gillett N, Fish EN (1995) Chemokine expression in rheumatoid arthritis (RA): evidence of RANTES and macrophage inflammatory protein (MIP)-1 beta production by synovial T cells. Clin Exp Immunol 101:398–407

    Article  PubMed  CAS  Google Scholar 

  22. Volin MV, Shah MR, Tokuhira M, Haines GK, Woods JM, Koch AE (1998) RANTES expression and contribution to monocyte chemotaxis in arthritis. Clin Immunol Immunopathol 89:44–53

    Article  PubMed  CAS  Google Scholar 

  23. Boiardi L, Macchioni P, Meliconi R, Pulasatelli L, Facchini A, Salvarani C (1999) Relationship between serum RANTES levels and radiological progression in rheumatoid arthritis patients treated with methotrexate. Clin Exp Rheumatol 17:419–425

    PubMed  CAS  Google Scholar 

  24. Kuna P, Reddigari SR, Shall TJ et al (1992) RANTES, a monocyte and T lymphocyte chemotactic cytokine releases histamine from human basophils. J Immunol 149:636–642

    PubMed  CAS  Google Scholar 

  25. Rot A, Krieger M, Brunner T et al (1992) RANTES and macrophage inflammatory protein 1α induce the migration and activation of normal human eosinophil granulocytes. J Exp Med 176:1489–1495

    Article  PubMed  CAS  Google Scholar 

  26. Wolpe SD, Cerami A (1989) Macrophage inflammatory protein 1 and 2: members of a novel superfamily of cytokines. FASEB J 3:2565–2573

    PubMed  CAS  Google Scholar 

  27. Taub DD, Colon K, Lloyd AR et al (1993) Preferential migration of activated CD4α and CD8β T cells in response to MIP-1α and MIP-1β. Science 260:355–358

    Article  PubMed  CAS  Google Scholar 

  28. Plater-Zyberk C, Hoogewerf AJ, Proudfoot AE, Power CA et al (1997) Effect of a CC chemokine receptor antagonist on collagen induced arthritis in DBA/1 mice. Immunol Lett 57:117–120

    Article  PubMed  CAS  Google Scholar 

  29. Yang YF, Mukai T, Yamaguchi N et al (2002) A non-peptide CCR5 antagonist inhibits collagen-induced arthritis by modulating T cell migration without affecting anti-collagen T cell responses. Eur J Immunol 32:2124–2132

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Eiji Torikai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Torikai, E., Kageyama, Y., Suzuki, M. et al. The effect of infliximab on chemokines in patients with rheumatoid arthritis. Clin Rheumatol 26, 1088–1093 (2007). https://doi.org/10.1007/s10067-006-0453-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-006-0453-5

Keywords

Navigation