Skip to main content

Advertisement

Log in

The distinct expressions of interleukin-15 and interleukin-15 receptor α in Behçet’s disease

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

Abstract

Interleukin-15 (IL-15) is a pleotrophic cytokine that is involved in the pathogenesis of diverse inflammatory rheumatic diseases. The aims of this study were to compare serum IL-15 levels and expression of its receptor (IL-15Rα) in Behçet’s disease (BD) with those in other rheumatic diseases and to identify the relationship between serum IL-15 levels and various clinical parameters in BD. One hundred fifty-eight subjects consisting of 40 BD, 38 systemic lupus erythematosus (SLE), 40 rheumatoid arthritis (RA), and 40 healthy controls were enrolled. Serum IL-15 levels were measured using an enzyme-linked immunosorbent assay. The proportion of IL-15Rα expression on each leukocyte subset was measured by flow cytometry. Erythrocyte sediment rate (ESR) and C-reactive protein (CRP) were measured for each enrolled subject. The clinical activity index of BD was assessed for BD patients. Serum IL-15 levels in BD patients are significantly higher than those of healthy controls, SLE, and RA patients (p < 0.001, p < 0.001, and p < 0.001, respectively). Serum IL-15 levels in BD were closely related to ESR (r = 0.405, p = 0.027), but not to CRP or the clinical activity index of BD (p > 0.05 for both). Additionally, there was no difference in serum IL-15 levels between active and inactive disease states in BD (p > 0.05). The proportion of IL-15Rα expression on total leukocytes was much lower for all rheumatic diseases, including BD, than in healthy controls (p < 0.01 for SLE, p < 0.01 for RA, and p < 0.05 for BD). IL-15 and IL-15Rα system may be involved in the inflammatory process and pathogenesis of BD.

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. Sakane T, Takeno M, Suzuki N, Inaba G (1999) Behcet’s disease. N Engl J Med 341:1284–1291

    Article  PubMed  CAS  Google Scholar 

  2. Suzuki Y, Hoshi K, Matsuda T, Mizushima Y (1992) Increased peripheral blood γδ+ T cells and natural killer cells in Behçet’s disease. J Rheumatol 19:588–592

    PubMed  CAS  Google Scholar 

  3. Yu HG, Lee DS, Seo JM, Ahn JK, Yu YS, Lee WJ et al (2004) The number of CD8+ T cells and NKT cells increases in the aqueous humor of patients with Behçet’s uveitis. Clin Exp Immunol 137:437–443

    Article  PubMed  CAS  Google Scholar 

  4. Sahin S, Akoğlu T, Direskeneli H, Sen LS, Lawrence R (1996) Neutrophil adhesion to endothelial cells and factors affecting adhesion in patients with Behçet’s disease. Ann Rheum Dis 55:128–133

    Article  PubMed  CAS  Google Scholar 

  5. Zouboulis CC, Katsantonis J, Ketteler R, Treudler R, Kaklamani E, Hornemann S et al (2000) Adamantiades-Behçet’s disease: interleukin-8 is increased in serum of patients with active oral and neurological manifestations and is secreted by small vessel endothelial cells. Arch Dermatol Res 292:279–284

    Article  PubMed  CAS  Google Scholar 

  6. Evereklioglu C, Er H, Türköz Y, Cekmen M (2002) Serum levels of TNF-α, sIL-2R, IL-6, and IL-8 are increased and associated with elevated lipid peroxidation in patients with Behçet’s disease. Mediators Inflamm 11:87–93

    Article  PubMed  CAS  Google Scholar 

  7. Grabstein KH, Eisenman J, Shanebeck K, Rauch C, Srinivasan S, Fung V et al (1994) Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor. Science 264:965–968

    Article  PubMed  CAS  Google Scholar 

  8. Waldmann TA, Tagaya Y (1999) The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens. Annu Rev Immunol 17:19–49

    Article  PubMed  CAS  Google Scholar 

  9. Stonier SW, Schluns KS (2010) Trans-presentation: a novel mechanism regulating IL-15 delivery and responses. Immunol Lett 127:85–92

    Article  PubMed  CAS  Google Scholar 

  10. Dubois S, Mariner J, Waldmann TA, Tagaya Y (2002) IL-15Rα recycles and presents IL-15 In trans to neighboring cells. Immunity 17:537–547

    Article  PubMed  CAS  Google Scholar 

  11. Gonzalez-Alvaro I, Ortiz AM, Garcia-Vicuña R, Balsa A, Pascual-Salcedo D, Laffon A (2003) Increased serum levels of interleukin-15 in rheumatoid arthritis with long- term disease. Clin Exp Rheumatol 21:639–642

    PubMed  CAS  Google Scholar 

  12. McInnes IB, Leung BP, Sturrock RD, Field M, Liew FY (1997) Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-α production in rheumatoid arthritis. Nat Med 3:189–195

    Article  PubMed  CAS  Google Scholar 

  13. Suzuki J, Morimoto S, Amano H, Tokano Y, Takasaki Y, Hashimoto H (2001) Serum levels of interleukin 15 in patients with rheumatic diseases. J Rheumatol 28:2389–2391

    PubMed  CAS  Google Scholar 

  14. Baranda L, de la Fuente H, Layseca-Espinosa E, Portales-Pérez D, Niño-Moreno P, Valencia-Pacheco G et al (2005) IL-15 and IL-15R in leucocytes from patients with systemic lupus erythematosus. Rheumatology (Oxford) 44:1507–1513

    Article  CAS  Google Scholar 

  15. Curnow SJ, Pryce K, Modi N, Knight B, Graham EM, Stewart JE et al (2008) Serum cytokine profiles in Behçet’s disease: is there a role for IL-15 in pathogenesis? Immunol Lett 121:7–12

    Article  PubMed  CAS  Google Scholar 

  16. Hamzaoui K, Hamzaoui A, Ghorbel I, Khanfir M, Houman H (2006) Levels of IL-15 in serum and cerebrospinal fluid of patients with Behçet’s disease. Scand J Immunol 64:655–660

    Article  PubMed  CAS  Google Scholar 

  17. Ahn JK, Yu HG, Chung H, Park YG (2006) Intraocular cytokine environment in active Behçet uveitis. Am J Ophthalmol 142:429–434

    Article  PubMed  CAS  Google Scholar 

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

    Google Scholar 

  19. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277

    Article  PubMed  CAS  Google Scholar 

  20. Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classifi cation of systemic lupus erythematosus. Arthritis Rheum 40:1725

    Article  PubMed  CAS  Google Scholar 

  21. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324

    Article  PubMed  CAS  Google Scholar 

  22. Fresko I, Soy M, Hamuryudan V, Yurdakul S, Yavuz S, Tümer Z et al (1998) Genetic anticipation in Behçet’s syndrome. Ann Rheum Dis 57:45–48

    Article  PubMed  CAS  Google Scholar 

  23. Hirohata S, Oka H, Mizushima Y (1992) Streptococcal-related antigens stimulate production of IL6 and interferon-gamma by T cells from patients with Behcet’s disease. Cell Immunol 140:410–419

    Article  PubMed  CAS  Google Scholar 

  24. García VE, Jullien D, Song M, Uyemura K, Shuai K, Morita CT et al (1998) IL-15 enhances the response of human γδ T cells to nonpeptide microbial antigens. J Immunol 160:4322–4329

    PubMed  Google Scholar 

  25. Jullien D, Sieling PA, Uyemura K, Mar ND, Rea TH, Modlin RL (1997) IL-15, an immunomodulator of T cell responses in intracellular infection. J Immunol 158:800–806

    PubMed  CAS  Google Scholar 

  26. Oppenheimer-Marks N, Brezinschek RI, Mohamadzadeh M, Vita R, Lipsky PE (1998) Interleukin 15 is produced by endothelial cells and increases the transendothelial migration of T cells In vitro and in the SCID mouse-human rheumatoid arthritis model In vivo. J Clin Invest 101:1261–1272

    Article  PubMed  CAS  Google Scholar 

  27. Matsumoto K, Ohi H, Kanmatsuse K (1999) Effects of interleukin-15 on vascular permeability factor release by peripheral blood mononuclear cells in normal subjects and in patients with minimal-change nephrotic syndrome. Nephron 82:32–38

    Article  PubMed  CAS  Google Scholar 

  28. Aringer M, Stummvoll GH, Steiner G, Köller M, Steiner CW, Höfler E (2001) Serum interleukin-15 is elevated in systemic lupus erythematosus. Rheumatology (Oxford) 40:876–881

    Article  CAS  Google Scholar 

  29. Giri JG, Kumaki S, Ahdieh M, Friend DJ, Loomis A, Shanebeck K (1995) Identification and cloning of a novel IL-15 binding protein that is structurally related to the alpha chain of the IL-2 receptor. EMBO J 14:3654–3663

    PubMed  CAS  Google Scholar 

  30. Mortier E, Woo T, Advincula R, Gozalo S, Ma A (2008) IL-15Ralpha chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation. J Exp Med 205:1213–1225

    Article  PubMed  CAS  Google Scholar 

  31. Mortier E, Bernard J, Plet A, Jacques Y (2004) Natural, proteolytic release of a soluble form of human IL-15 receptor alpha-chain that behaves as a specific, high affinity IL-15 antagonist. J Immunol 173:1681–1688

    PubMed  CAS  Google Scholar 

  32. Verri WA Jr, Cunha TM, Ferreira SH, Wei X, Leung BP, Fraser A (2007) IL-15 mediates antigen-induced neutrophil migration by triggering IL-18 production. Eur J Immunol 37:3373–3380

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

Not declared.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Seong-Kyu Kim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Choe, JY., Lee, H., Kim, S.G. et al. The distinct expressions of interleukin-15 and interleukin-15 receptor α in Behçet’s disease. Rheumatol Int 33, 2109–2115 (2013). https://doi.org/10.1007/s00296-013-2705-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-013-2705-4

Keywords

Navigation