J Korean Med Sci.  2013 Sep;28(9):1289-1292. 10.3346/jkms.2013.28.9.1289.

Caspase-1 Level in Synovial Fluid Is High in Patients with Spondyloarthropathy but Not in Patients with Gout

• Son CN
• Bang SY
• Kim JH
• Choi CB
• Kim TH
• Jun JB

• KMID: 1793042
• DOI: http://doi.org/10.3346/jkms.2013.28.9.1289

Abstract

Activation of caspase-1 by NALP3 inflammasomes has been shown to be important in initiating acute gouty arthritis. The objectives of this study were to measure the levels of caspase-1 in synovial fluid in gout and various arthritides, and to elucidate the clinical significance of caspase-1 levels in synovial fluid. Caspase-1, IL-1beta, IL-18, and uric acid were measured in synovial fluid from 112 patients with gout and other arthritides, such as rheumatoid arthritis, osteoarthritis, and spondyloarthropathy. Caspase-1 in synovial fluid from patients with crystal-induced arthritis, inflammatory arthritis, osteoarthritis, and spondyloarthropathy was 35.9 +/- 86.7, 49.7 +/- 107.7, 2.1 +/- 7.0, and 152.6 +/- 155.7 pg/mL, respectively. The mean level and the frequency of high levels (> or =125 pg/mL) of caspase-1 in spondyloarthropathy were significantly higher than those in the other arthritides including gout. Caspase-1 was detectible in the synovial fluid of patients with the various arthritides. Contrary to our hypothesis, the caspase-1 level in the synovial fluid of patients with gout was not higher than in that of other arthritides. High levels of caspase-1 may be helpful in differentiating spondyloarthropathy from other arthritides.

Keyword

Caspase-1; Synovial Fluid; Gout; Spondyloarthropathies

MeSH Terms

Adult
Aged
Arthritis, Rheumatoid/enzymology/metabolism/pathology
Caspase 1/*analysis
Female
Gout/*enzymology/metabolism/pathology
Humans
Interleukin-18/analysis
Interleukin-1beta/analysis
Leukocyte Count
Male
Middle Aged
Osteoarthritis/enzymology/metabolism/pathology
Spondylarthropathies/*enzymology/metabolism/pathology
Synovial Fluid/*enzymology/metabolism
Uric Acid/analysis
Caspase 1
Interleukin-18
Interleukin-1beta
Uric Acid

Reference

1. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 2011; 63:3136–3141.

2. Agudelo CA, Wise CM. Gout: diagnosis, pathogenesis, and clinical manifestations. Curr Opin Rheumatol. 2001; 13:234–239.

3. Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006; 440:237–241.

4. Church LD, Cook GP, McDermott MF. Primer: inflammasomes and interleukin 1beta in inflammatory disorders. Nat Clin Pract Rheumatol. 2008; 4:34–42.

5. Franciotta D, Martino G, Zardini E, Furlan R, Bergamaschi R, Gironi M, Bergami A, Angelini G, De Benedetti F, Pignatti P, et al. Caspase-1 levels in biological fluids from patients with multiple sclerosis and from patients with other neurological and non-neurological diseases. Eur Cytokine Netw. 2002; 13:99–103.

6. Wallace SL, Robinson H, Masi AT, Decker JL, McCarty DJ, Yü TF. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum. 1977; 20:895–900.

7. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988; 31:315–324.

8. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982; 25:1271–1277.

9. Van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosi`ng spondylitis: a proposal for modification of the New York criteria. Arthritis Rheum. 1984; 27:361–368.

10. Scanu A, Oliviero F, Ramonda R, Frallonardo P, Dayer JM, Punzi L. Cytokine levels in human synovial fluid during the different stages of acute gout: role of transforming growth factor β1 in the resolution phase. Ann Rheum Dis. 2012; 71:621–624.

11. Scanzello CR, Umoh E, Pessler F, Diaz-Torne C, Miles T, Dicarlo E, Potter HG, Mandl L, Marx R, Rodeo S, et al. Local cytokine profiles in knee osteoarthritis: elevated synovial fluid interleukin-15 differentiates early from end-stage disease. Osteoarthritis Cartilage. 2009; 17:1040–1048.

12. Denoble AE, Huffman KM, Stabler TV, Kelly SJ, Hershfield MS, McDaniel GE, Coleman RE, Kraus VB. Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation. Proc Natl Acad Sci U S A. 2011; 108:2088–2093.

13. Shao XT, Feng L, Gu LJ, Wu LJ, Feng TT, Yang YM, Wu NP, Yao HP. Expression of interleukin-18, IL-18BP, and IL-18R in serum, synovial fluid, and synovial tissue in patients with rheumatoid arthritis. Clin Exp Med. 2009; 9:215–221.

14. Bokarewa M, Hultgren O. Is interleukin-18 useful for monitoring rheumatoid arthritis? Scand J Rheumatol. 2005; 34:433–436.

15. Guma M, Ronacher L, Liu-Bryan R, Takai S, Karin M, Corr M. Caspase 1-independent activation of interleukin-1beta in neutrophil-predominant inflammation. Arthritis Rheum. 2009; 60:3642–3650.

16. Joosten LA, Netea MG, Fantuzzi G, Koenders MI, Helsen MM, Sparrer H, Pham CT, van der Meer JW, Dinarello CA, van den Berg WB. Inflammatory arthritis in caspase 1 gene-deficient mice: contribution of proteinase 3 to caspase 1-independent production of bioactive interleukin-1beta. Arthritis Rheum. 2009; 60:3651–3662.

17. Rosengren S, Hoffman HM, Bugbee W, Boyle DL. Expression and regulation of cryopyrin and related proteins in rheumatoid arthritis synovium. Ann Rheum Dis. 2005; 64:708–714.

18. Kolly L, Busso N, Palmer G, Talabot-Ayer D, Chobaz V, So A. Expression and function of the NALP3 inflammasome in rheumatoid synovium. Immunology. 2010; 129:178–185.

19. Baeten D, Kruithof E, De Rycke L, Boots AM, Mielants H, Veys EM, De Keyser F. Infiltration of the synovial membrane with macrophage subsets and polymorphonuclear cells reflects global disease activity in spondyloarthropathy. Arthritis Res Ther. 2005; 7:R359–R369.

20. Busso N, So A. Mechanisms of inflammation in gout. Arthritis Res Ther. 2010; 12:206.

21. Baeten D, Demetter P, Cuvelier CA, Kruithof E, Van Damme N, De Vos M, Veys EM, De Keyser F. Macrophages expressing the scavenger receptor CD163: a link between immune alterations of the gut and synovial inflammation in spondyloarthropathy. J Pathol. 2002; 196:343–350.

22. François RJ, Gardner DL, Degrave EJ, Bywaters EG. Histopathologic evidence that sacroiliitis in ankylosing spondylitis is not merely enthesitis. Arthritis Rheum. 2000; 43:2011–2024.

23. Demetter P, De Vos M, Van Huysse JA, Baeten D, Ferdinande L, Peeters H, Mielants H, Veys EM, De Keyser F, Cuvelier CA. Colon mucosa of patients both with spondyloarthritis and Crohn's disease is enriched with macrophages expressing the scavenger receptor CD163. Ann Rheum Dis. 2005; 64:321–324.

24. Chou CT. Why is biologic therapy useful in spondyloarthritis? knowledge from synovial immunopathologic studies of spondyloarthritis. Int J Rheum Dis. 2012; 15:507–511.