Skip to main content


Log in

Synovial angiostatic non-ELR CXC chemokines in inflammatory arthritides: does CXCL4 designate chronicity of synovitis?

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


In our previous studies, we found higher synovial fluid (SF) levels of angiogenic ELR(+) CXC chemokines such as CXCL1, CXCL5, CXCL6 and CXCL8, which play an important role in neutrophil migration and angiogenesis, and more abundant synovial CXCR2 chemokine receptor expression in patients with rheumatoid arthritis (RA) than those with Behçet’s disease (BD), familial Mediterranean fever and osteoarthritis (OA). As a continuation of our previous studies, we investigated synovial levels of angiostatic non-ELR CXC chemokines (CXCL4, CXCL9 and CXCL10) in patients with RA, BD, spondyloarthritis (SpA), and OA. Seventy (17 RA, 15 BD, 19 SpA, and 19 OA) patients were enrolled in the study. The levels of CXCL4, CXCL9, and CXCL10 were measured by ELISA. The SF levels of CXCL4 in patients with RA were higher than those of the patients with BD, SpA, and OA (P = 0.007, P = 0.022, and P = 0.017, respectively). No difference was found with respect to CXCL4 levels among the BD, SpA, and OA patients. The synovial CXCL9 levels of patients with RA and SpA were found to be higher than those of the patients with OA (P = 0.002 and P = 0.005, respectively), while no statistically significant difference was detected among the other groups. With regard to SF CXCL10 levels, patients with RA had higher levels as compared to patients with OA (P = 0.002), but no significant difference was found among the other groups. CXCL9 correlated with CXCL4 and CXCL10 (P < 0.05 for both) in patients with RA. No correlation was found in other parameters. The angiostatic non-ELR CXC chemokines were expressed in synovial inflammation. We proposed that angiostatic non-ELR CXC chemokines may increase to balance angiogenic ELR (+) CXC chemokines in which increased levels were shown in patients with inflammatory arthritides and CXCL4 may contribute to designate the chronicity of synovitis in patients with RA. In addition, as CXCL-9 and CXCL-10 play crucial role in inflammation characterized by Th1 polarization, we suggested that they may contribute to the commencement and the perpetuation of synovitis seen in these groups of arthritides.

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

Similar content being viewed by others


  1. Manzo A, Caporali R, Montecucco C, Pitzalis C (2003) Role of chemokines and chemokine receptors in regulating specific leukocyte trafficking in immune/inflammatory response. Clin Exp Rheumatol 21:501–508

    PubMed  CAS  Google Scholar 

  2. Vergunst CE, Tak PP (2005) Chemokines: their role in rheumatoid arthritis. Curr Rheumatol Rep 7:382–388

    Article  PubMed  CAS  Google Scholar 

  3. Strieter RM, Burdick MD, Gomperts BN, Belperio JA, Keane MP (2005) CXC chemokines in angiogenesis. Cytokine Growth Factor Rev 16:593–609

    Article  PubMed  CAS  Google Scholar 

  4. Strieter RM, Polverini PJ, Kunkel SL, Arenberg DA, Burdick MD, Kasper J et al (1995) The functional role of ELR motif in CXC chemokine-mediated angiogenesis. J Biol Chem 270:27348–27357

    Article  PubMed  CAS  Google Scholar 

  5. Pay S, Erdem H, Serdar M, Dinç A, Şimşek İ, Turan M (2002) Comparison of synovial MMP-1 and TIMP-1 levels in patients with various inflammatory arthritides: is there any difference between rheumatoid arthritis, Behçet’s disease and familial Mediterranean fever? Clin Rheumatol 21:511–515

    Article  PubMed  CAS  Google Scholar 

  6. Pay S, Erdem H, Pekel A, Simsek I, Musabak U, Sengul A, Dinc A (2005) Synovial Proinflammatory cytokines and their correlation with matrix metalloproteinase-3 expression in Behçet’s disease. Does interleukin-1β play a major role in Behçet’s Synovitis? Rheumatol Int. (Online)

  7. Erdem H, Pay S, Serdar M, Şimşek İ, Dinç A, Muşabak U, Pekel A, Turan M (2005) Different ELR (+) angiogenic CXC chemokine profiles in synovial fluid of patients with Behçet’s disease, familial Mediterranean fever, rheumatoid arthritis, and osteoarthritis. Rheumatol Int 26:162–167

    Article  PubMed  CAS  Google Scholar 

  8. Pay S, Musabak U, Simsek İ, Pekel A, Erdem H, Dinç A, Şengül A (2005) Expression of CXCR-1 and CXCR-2 chemokine receptors on synovial neutrophils in inflammatory arthritides: does persistent or increasing expression of CXCR2 contribute to the chronic inflammation or erosive changes? Annual European Congress on Rheumatology-EULAR 2005, 7–11 June 2005

  9. Calabrese LH, Michel BA, Bloch DA (1990) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 33:1108–1113

    Article  PubMed  CAS  Google Scholar 

  10. International Study Group for Behcet’s Disease (1990) Criteria for diagnosis of Behcet’s disease. Lancet 335:1078–1080

    Google Scholar 

  11. Dougados M, van der Linden S, Juhlin R, Huitfeldt B, Amor B, Calin A et al (1991) The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum 34:1218–1227

    Article  PubMed  CAS  Google Scholar 

  12. Altman RD (1991) Criteria for classification of clinical osteoarthritis. J Rheumatol 18:10–12

    Google Scholar 

  13. Rudolph EH, Woods JM (2005) Chemokine expression and regulation of angiogenesis in rheumatoid arthritis. Curr Pharm Des 11:613–631

    Article  PubMed  CAS  Google Scholar 

  14. Romagnani P, Lasagni L, Anniziato F, Serio M, Romagnani S (2004) CXC chemokines: the regulatory link between inflammation and angiogenesis. Trends Immunol 25:200–209

    Article  CAS  Google Scholar 

  15. Rosenkilde MM, Schwartz TW (2004) The chemokine system—a major regulator of angiogenesis in health and disease. APMIS 112:481–495

    Article  PubMed  CAS  Google Scholar 

  16. Koch AE, Volin MV, Woods JM, Kunkel SL, Connors MA, Harlow LA et al (2001) Regulation of angiogenesis by the CXC chemokines interleukine-8 and epithelial neutrophil activating peptide 78 in the rheumatoid joint. Arthritis Rheum 44:31–40

    Article  PubMed  CAS  Google Scholar 

  17. Patel DD, Zachariah JP, Whichard LP (2001) CXCR3 and CCR5 ligands in rheumatoid arthritis synovium. Clin Immunol 98:39–45

    Article  PubMed  CAS  Google Scholar 

  18. Strieter RM, Belperio JA, Burdick MD, Keane MP (2005) CXC chemokines in angiogenesis relevant to chronic fibroproliferation. Curr Drug Targets İnflamm Allergy 4:23–26

    Article  PubMed  CAS  Google Scholar 

  19. Moser B, Loetscher P (2001) Lymphocyte traffic control by chemokines. Nat Immunol 2:1–7

    Article  CAS  Google Scholar 

  20. Esche C, Stellato C, Beck LA (2005) Chemokines: key players in innate and adaptive immunity. J Invest Dermatol 125:615–628

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Salih Pay.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Erdem, H., Pay, S., Musabak, U. et al. Synovial angiostatic non-ELR CXC chemokines in inflammatory arthritides: does CXCL4 designate chronicity of synovitis?. Rheumatol Int 27, 969–973 (2007).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: