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Correlation between plasma, synovial fluid and articular cartilage Interleukin-18 with radiographic severity in 33 patients with osteoarthritis of the knee

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Abstract

Osteoarthritis (OA) is a complex disease characterized by cartilage degeneration, secondary synovial membrane inflammation and subchondral bone changes. In recent years, many studies have confirmed that interleukin-18 (IL-18) is involved in the inflammatory process of inflammatory joint diseases. In the present study, we investigated IL-18 levels in plasma, synovial fluid and articular cartilage of patients with primary knee OA (n = 33) to analyze their relationship with radiographic severity. Compared to healthy controls (n = 15), OA patients had higher plasma and synovial fluid IL-18 concentrations (45.8 ± 22.1 vs. 23.7 ± 13.6 pg/ml, P < 0.001 and 75.2 ± 40.1 vs. 28.3 ± 11.6 pg/ml, P < 0.001) as measured by enzyme-linked immunosorbent assay. Also, the percentage of immunofluorescent IL-18 positive cells in articular cartilage was significantly increased in OA compared to controls (46.5 ± 10.3 vs. 2.9 ± 1.7, P < 0.001). Moreover, plasma, synovial fluid and articular cartilage IL-18 significantly positively correlated with radiographic severity, respectively (r = 0.663, P < 0.001, r = 0.56, P = 0.001 and r = 0.884, P < 0.001). Subsequent analysis revealed that plasma, synovial fluid and articular cartilage IL-18 levels positively correlated with each other (r = 0.632, P < 0.001, r = 0.489, P = 0.004 and r = 0.620, P < 0.001). These data suggested that plasma, synovial fluid and articular cartilage IL-18 levels were significantly increased in OA patients, and these elevated levels were positively correlated with radiographic severity. Accordingly, our study supports the role of IL-18 in the pathophysiology of OA.

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References

  1. Palmieri B, Lodi D, Capone S (2010) Osteoarthritis and degenerative joint disease: local treatment options update. Acta Biomed 81:94–100

    CAS  PubMed  Google Scholar 

  2. Bijlsma JW, Berenbaum F, Lafeber FP (2011) Osteoarthritis: an update with relevance for clinical practice. Lancet 377:2115–2126

    Article  PubMed  Google Scholar 

  3. Mehta VB, Hart J, Wewers MD (2001) ATP-stimulated release of interleukin (IL)-1beta and IL-18 requires priming by lipopolysaccharide and is independent of caspase-1 cleavage. J Biol Chem 276:3820–3826

    Article  CAS  PubMed  Google Scholar 

  4. Nakanishi K, Yoshimoto T, Tsutsui H, Okamura H (2001) Interleukin-18 regulates both Th1 and Th2 responses. Annu Rev Immunol 19:423–474

    Article  CAS  PubMed  Google Scholar 

  5. Olee T, Hashimoto S, Quach J, Lotz M (1999) IL-18 is produced by articular chondrocytes and induces proinflammatory and catabolic responses. J Immunol 162:1096–1100

    CAS  PubMed  Google Scholar 

  6. Wittmann M, Purwar R, Hartmann C, Gutzmer R, Werfel T (2005) Human keratinocytes respond to interleukin-18: implication for the course of chronic inflammatory skin diseases. J Invest Dermatol 124:1225–1233

    Article  CAS  PubMed  Google Scholar 

  7. Udagawa N, Horwood NJ, Elliott J, Mackay A, Owens J, Okamura H, Kurimoto M, Chambers TJ, Martin TJ, Gillespie MT (1997) Interleukin-18 (interferon-gamma-inducing factor) is produced by osteoblasts and acts via granulocyte/macrophage colony-stimulating factor and not via interferon-gamma to inhibit osteoclast formation. J Exp Med 185:1005–1012

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Wei XQ, Leung BP, Arthur HM, McInnes IB, Liew FY (2001) Reduced incidence and severity of collagen-induced arthritis in mice lacking IL-18. J Immunol 166:517–521

    Article  CAS  PubMed  Google Scholar 

  9. Hung J, McQuillan BM, Chapman CM, Thompson PL, Beilby JP (2005) Elevated interleukin-18 levels are associated with the metabolic syndrome independent of obesity and insulin resistance. Arterioscler Thromb Vasc Biol 25:1268–1273

    Article  CAS  PubMed  Google Scholar 

  10. Dai SM, Shan ZZ, Xu H, Nishioka K (2007) Cellular targets of interleukin-18 in rheumatoid arthritis. Ann Rheum Dis 66:1411–1418

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Akira S (2000) The role of IL-18 in innate immunity. Curr Opin Immunol 12:59–63

    Article  CAS  PubMed  Google Scholar 

  12. Kawase Y, Hoshino T, Yokota K, Kuzuhara A, Kirii Y, Nishiwaki E, Maeda Y, Takeda J, Okamoto M, Kato S, Imaizumi T, Aizawa H, Yoshino K (2003) Exacerbated and prolonged allergic and non-allergic inflammatory cutaneous reaction in mice with targeted interleukin-18 expression in the skin. J Invest Dermatol 121:502–509

    Article  CAS  PubMed  Google Scholar 

  13. Okamoto M, Kato S, Oizumi K, Kinoshita M, Inoue Y, Hoshino K, Akira S, McKenzie AN, Young HA, Hoshino T (2002) Interleukin 18 (IL-18) in synergy with IL-2 induces lethal lung injury in mice: a potential role for cytokines, chemokines, and natural killer cells in the pathogenesis of interstitial pneumonia. Blood 99:1289–1298

    Article  CAS  PubMed  Google Scholar 

  14. Petrovic-Rackov L, Pejnovic N (2006) Clinical significance of IL-18, IL-15, IL-12 and TNF-alpha measurement in rheumatoid arthritis. Clin Rheumatol 25:448–452

    Article  PubMed  Google Scholar 

  15. Futani H, Okayama A, Matsui K, Kashiwamura S, Sasaki T, Hada T, Nakanishi K, Tateishi H, Maruo S, Okamura H (2002) Relation between interleukin-18 and PGE2 in synovial fluid of osteoarthritis: a potential therapeutic target of cartilage degradation. J Immunother 25(Suppl 1):S61–S64

    Article  CAS  PubMed  Google Scholar 

  16. Takei S, Hoshino T, Matsunaga K, Sakazaki Y, Sawada M, Oda H, Takenaka S, Imaoka H, Kinoshita T, Honda S, Ida H, Fukuda TA, Aizawa H (2011) Soluble interleukin-18 receptor complex is a novel biomarker in rheumatoid arthritis. Arthritis Res Ther 13:R52

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Dai SM, Shan ZZ, Nishioka K, Yudoh K (2005) Implication of interleukin 18 in production of matrix metalloproteinases in articular chondrocytes in arthritis: direct effect on chondrocytes may not be pivotal. Ann Rheum Dis 64:735–742

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Plater-Zyberk C, Joosten LA, Helsen MM, Sattonnet-Roche P, Siegfried C, Alouani S, van De Loo FA, Graber P, Aloni S, Cirillo R, Lubberts E, Dinarello CA, van Den Berg WB, Chvatchko Y (2001) Therapeutic effect of neutralizing endogenous IL-18 activity in the collagen-induced model of arthritis. J Clin Invest 108:1825–1832

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Joosten LA, Radstake TR, Lubberts E, van den Bersselaar LA, van Riel PL, van Lent PL, Barrera P, van den Berg WB (2003) Association of interleukin-18 expression with enhanced levels of both interleukin-1 beta and tumor necrosis factor alpha in knee synovial tissue of patients with rheumatoid arthritis. Arthritis Rheum 48:339–347

    Article  CAS  PubMed  Google Scholar 

  20. Peng CZ, Cao JM, Xiao T, Peng C, Yang HB, Chen X, Fang JZ (2006) Concentration of IL-18 and PGE2 in synovial fluid in patients with osteoarthritis and its significance. Zhong Nan Da Xue Xue Bao Yi Xue Ban 31:862–865

    CAS  PubMed  Google Scholar 

  21. Fu Z, Liu P, Yang D, Wang F, Yuan L, Lin Z, Jiang J (2012) Interleukin-18-induced inflammatory responses in synoviocytes and chondrocytes from osteoarthritic patients. Int J Mol Med 30:805–810

    CAS  PubMed  Google Scholar 

  22. Kellgren JH, Lawrence JS (1957) Radiological assessment of osteo-arthrosis. Ann Rheum Dis 16:494–502

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Pelletier JP, Lascau-Coman V, Jovanovic D, Fernandes JC, Manning P, Connor JR, Currie MG, Martel-Pelletier J (1999) Selective inhibition of inducible nitric oxide synthase in experimental osteoarthritis is associated with reduction in tissue levels of catabolic factors. J Rheumatol 26:2002–2014

    CAS  PubMed  Google Scholar 

  24. Rooney T, Murphy E, Benito M, Roux-Lombard P, FitzGerald O, Dayer JM, Bresnihan B (2004) Synovial tissue interleukin-18 expression and the response to treatment in patients with inflammatory arthritis. Ann Rheum Dis 63:1393–1398

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Inoue H, Hiraoka K, Hoshino T, Okamoto M, Iwanaga T, Zenmyo M, Shoda T, Aizawa H, Nagata K (2008) High levels of serum IL-18 promote cartilage loss through suppression of aggrecan synthesis. Bone 42:1102–1110

    Article  CAS  PubMed  Google Scholar 

  26. Kinds MB, Welsing PM, Vignon EP, Bijlsma JW, Viergever MA, Marijnissen AC, Lafeber FP (2011) A systematic review of the association between radiographic and clinical osteoarthritis of hip and knee. Osteoarthritis Cartilage 19:768–778

    Article  CAS  PubMed  Google Scholar 

  27. van der Sluijs JA, Geesink RG, van der Linden AJ, Bulstra SK, Kuyer R, Drukker J (1992) The reliability of the Mankin score for osteoarthritis. J Orthop Res 10:58–61

    Article  PubMed  Google Scholar 

  28. DeGroot J, Bank RA, Tchetverikov I, Verzijl N, TeKoppele JM (2002) Molecular markers for osteoarthritis: the road ahead. Curr Opin Rheumatol 14:585–589

    Article  CAS  PubMed  Google Scholar 

  29. van Spil WE, DeGroot J, Lems WF, Oostveen JC, Lafeber FP (2010) Serum and urinary biochemical markers for knee and hip-osteoarthritis: a systematic review applying the consensus BIPED criteria. Osteoarthritis Cartilage 18:605–612

    Article  PubMed  Google Scholar 

  30. de Lange-Brokaar BJ, Ioan-Facsinay A, van Osch GJ, Zuurmond AM, Schoones J, Toes RE, Huizinga TW, Kloppenburg M (2012) Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review. Osteoarthritis Cartilage 20:1484–1499

    Article  PubMed  Google Scholar 

  31. Neidhart M, Hauser N, Paulsson M, DiCesare PE, Michel BA, Hauselmann HJ (1997) Small fragments of cartilage oligomeric matrix protein in synovial fluid and serum as markers for cartilage degradation. Br J Rheumatol 36:1151–1160

    Article  CAS  PubMed  Google Scholar 

  32. Kinds MB, Marijnissen AC, Viergever MA, Emans PJ, Lafeber FP, Welsing PM (2013) Identifying phenotypes of knee osteoarthritis by separate quantitative radiographic features may improve patient selection for more targeted treatment. J Rheumatol 40:891–902

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Scientific Foundation of China Grant (No. 81171140), Natural Scientific Foundation of Jiangsu Province Grant (No. BK2009161), Projects of Nantong (BK2011013, BK2012075).

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Correspondence to Guicheng Huang.

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Wang, Y., Xu, D., Long, L. et al. Correlation between plasma, synovial fluid and articular cartilage Interleukin-18 with radiographic severity in 33 patients with osteoarthritis of the knee. Clin Exp Med 14, 297–304 (2014). https://doi.org/10.1007/s10238-013-0251-8

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  • DOI: https://doi.org/10.1007/s10238-013-0251-8

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