Skip to main content

Advertisement

SpringerLink
Log in

Cyclic adenosine 5′-monophosphate in synovial fluid of rheumatoid arthritis and osteoarthritis patients

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

Abstract

The relationship between synovial fluid (SF) cAMP level and IL-18 and PGE2 SF levels in rheumatoid arthritis (RA) and osteoarthritis (OA) patients, and between SF cAMP level and disease as well as inflammatory activity in RA were investigated in 17 RA and 19 OA patients. Erythrocyte sedimentation rate (ESR), serum (S) C-reactive protein (CRP) level and SF IL-18 level were higher in RA than in OA patients. SF PGE2 level was similar in both groups. SF cAMP level was higher in OA than in RA patients. In RA patients, SF cAMP level showed negative correlation with Disease Activity Score including a 28-joint count and S CRP, ESR and SF IL-18 level. The results suggest that cAMP promotes anti-inflammatory response in RA and OA patients, which is higher in the latter. Promotion of anti-inflammatory response by cAMP elevating agents might be useful in the treatment of RA.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Weyand CM, Goronzy JJ (2006) Pathomechanisms in rheumatoid arthritis—time for a string theory? J Clin Invest 116:869–871. doi:10.1172/JCI28300

    Article  PubMed  CAS  Google Scholar 

  2. Choy EH, Panayi GS (2001) Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 344:907–916. doi:10.1056/NEJM200103223441207

    Article  PubMed  CAS  Google Scholar 

  3. Dayer JM (1999) Interleukin-18, rheumatoid arthritis, and tissue destruction. J Clin Invest 104:1337–1339. doi:10.1172/JCI8731

    Article  PubMed  CAS  Google Scholar 

  4. Steiner G, Tohidast-Akrad M, Witzmann G et al (1999) Cytokine production by synovial T cells in rheumatoid arthritis. Rheumatology (Oxford) 38:202–213. doi:10.1093/rheumatology/38.3.202

    Article  CAS  Google Scholar 

  5. Manicourt DH, Poilvache P, Van Egeren A et al (2000) Synovial fluid levels of tumor necrosis factor alpha and oncostatin M correlate with levels of markers of the degradation of crosslinked collagen and cartilage aggrecan in rheumatoid arthritis but not in osteoarthritis. Arthritis Rheum 43:281–288. doi 10.1002/1529-0131(200002)43:2<281::AID-ANR7>3.0.CO;2-7

    Article  PubMed  CAS  Google Scholar 

  6. Yamamura M, Kawashima M, Taniai M et al (2001) Interferon-gamma-inducing activity of interleukin-18 in the joint with rheumatoid arthritis. Arthritis Rheum 44:275–285. doi 0.1002/1529-0131(200102)44:2<275::AID-ANR44>3.0.CO;2-B

    Article  PubMed  CAS  Google Scholar 

  7. 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. doi:10.1007/s10067-005-0106-0

    Article  PubMed  Google Scholar 

  8. Martel-Pelletier J, Pelletier JP, Fahmi H (2003) Cyclooxygenase-2 and prostaglandins in articular tissues. Semin Arthritis Rheum 33:155–167. doi:10.1016/S0049-0172(03)00134-3

    Article  PubMed  CAS  Google Scholar 

  9. Hishinuma T, Nakamura H, Sawai T et al (1999) Microdetermination of prostaglandin E2 in joint fluid in rheumatoid arthritis patients using gas chromatography/selected ion monitoring. Prostaglandins Other Lipid Mediat 58:179–186. doi:10.1016/S0090-6980(99)00028-3

    Article  PubMed  CAS  Google Scholar 

  10. Goto M, Hanyu T, Yoshio T et al (2001) Intra-articular injection of hyaluronate (SI-6601D) improves joint pain and synovial fluid prostaglandin E2 levels in rheumatoid arthritis: a multicenter clinical trial. Clin Exp Rheumatol 19:377–383

    PubMed  CAS  Google Scholar 

  11. Bertin P, Lapicque F, Payan E et al (1994) Sodium naproxen: concentration and effect on inflammatory response mediators in human rheumatoid synovial fluid. Eur J Clin Pharmacol 46:3–7. doi:10.1007/BF00195907

    Article  PubMed  CAS  Google Scholar 

  12. Seppälä E, Nissilä M, Isomäki H et al (1985) Comparison of the effects of different anti-inflammatory drugs on synovial fluid prostanoid concentrations in patients with rheumatoid arthritis. Clin Rheumatol 4:315–320. doi:10.1007/BF02031615

    Article  PubMed  Google Scholar 

  13. Elenkov IJ, Wilder RL, Chrousos GP et al (2000) The sympathetic nerve—an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev 52:595–638

    PubMed  CAS  Google Scholar 

  14. Moore AR, Willoughby DA (1995) The role of cAMP regulation in controlling inflammation. Clin Exp Immunol 101:387–389

    PubMed  CAS  Google Scholar 

  15. Wadskov S, Donde R, Sylvest J (1979) Plasma and synovial fluid cAMP in patients with rheumatoid arthritis. Scand J Rheumatol 8:136–138. doi:10.3109/03009747909114444

    Article  PubMed  CAS  Google Scholar 

  16. Trang LE, Lövgren O, Roch-Norlund AE et al (1979) Cyclic nucleotides in joint fluid in rheumatoid arthritis and in Reiter’s syndrome. Scand J Rheumatol 8:91–96. doi:10.3109/03009747909105343

    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. doi:10.1002/art.1780310302

    Article  PubMed  CAS  Google Scholar 

  18. http://www.das-score.nl/www.das-score.nl/index.html. Accessed 8 Sept 2007

  19. http://www.das-score.nl/www.das-score.nl/dasculators.html. Accessed 8 Sept 2007

  20. Ziolkowska M, Kurowska M, Radzikowska A et al (2002) High levels of osteoprotegerin and soluble receptor activator of nuclear factor kappa B ligand in serum of rheumatoid arthritis patients and their normalization after anti-tumor necrosis factor alpha treatment. Arthritis Rheum 46:1744–1753. doi:10.1002/art.10388

    Article  PubMed  CAS  Google Scholar 

  21. Fischbach F (1988) Laboratory diagnostic tests, 3rd edn. Lippincott, Philadelphia, pp 57–59

    Google Scholar 

  22. http://www.olympus-diagnostica.com/diagnostica/3112_marketinginformation.cfm. Accessed 8 Sept 2007

  23. http://www.rndsystems.com/pdf/7620.pdf. Accessed 8 Sept 2007

  24. http://www.assaydesigns.com/objects/catalog//product/extras/900-001.pdf. Accessed 8 Sept 2007

  25. http://www.assaydesigns.com/objects/catalog//product/extras/900-067.pdf. Accessed 8 Sept 2007

  26. Dawson B, Trapp RG (2001) Basic and clinical biostatistics, 3rd edn. Lange, New York

    Google Scholar 

  27. Hata AN, Breyer RM (2004) Pharmacology and signaling of prostaglandin receptors: multiple roles in inflammation and immune modulation. Pharmacol Ther 103:147–166. doi:10.1016/j.pharmthera.2004.06.003

    Article  PubMed  CAS  Google Scholar 

  28. Akaogi J, Nozaki T, Satoh M et al (2006) Role of PGE2 and EP receptors in the pathogenesis of rheumatoid arthritis and as a novel therapeutic strategy. Endocr Metab Immune Disord Drug Targets 6:383–394

    PubMed  CAS  Google Scholar 

  29. Min SY, Kim WU, Cho ML et al (2002) Prostaglandin E2 suppresses nuclear factor-kappaB mediated interleukin 15 production in rheumatoid synoviocytes. J Rheumatol 29:1366–1376

    PubMed  CAS  Google Scholar 

  30. Gomez PF, Pillinger MH, Attur M et al (2005) Resolution of inflammation: prostaglandin E2 dissociates nuclear trafficking ofindividual NF-kappaB subunits (p65, p50) in stimulated rheumatoid synovial fibroblasts. J Immunol 175:6924–6930

    PubMed  CAS  Google Scholar 

  31. Yacoubian S, Serhan CN (2007) New endogenous anti-inflammatory and proresolving lipid mediators: implications for rheumatic diseases. Nat Clin Pract Rheumatol 3:570–579. doi:10.1038/ncprheum0616

    Article  PubMed  CAS  Google Scholar 

  32. Gabay C (2006) Interleukin-6 and chronic inflammation. Arthritis Res Ther 8 (Suppl 2):S3. doi:10.1186/ar1917

  33. Baumann H, Kushner I (1998) Production of interleukin-6 by synovial fibroblasts in rheumatoid arthritis. Am J Pathol 152:641–644

    PubMed  CAS  Google Scholar 

  34. Dendorfer U, Oettgen P, Libermann TA (1994) Multiple regulatory elements in the interleukin-6 gene mediate induction by prostaglandins, cyclic AMP, and lipopolysaccharide. Mol Cell Biol 14:4443–4454

    PubMed  CAS  Google Scholar 

  35. Eigler A, Siegmund B, Emmerich U et al (1998) Anti-inflammatory activities of cAMP-elevating agents: enhancement of IL-10 synthesis and concurrent suppression of TNF production. J Leukoc Biol 63:101–107

    PubMed  CAS  Google Scholar 

  36. Kasyapa CS, Stentz CL, Davey MP et al (1999) Regulation of IL-15-stimulated TNF-alpha production by rolipram. J Immunol 163:2836–2843

    PubMed  CAS  Google Scholar 

  37. Souness JE, Griffin M, Maslen C et al (1996) Evidence that cyclic AMP phosphodiesterase inhibitors suppress TNF alpha generation from human monocytes by interacting with a ‘low-affinity’ phosphodiesterase 4 conformer. Br J Pharmacol 118:649–658

    PubMed  CAS  Google Scholar 

  38. Schillace RV, Carr DW (2006) The role of protein kinase A and A-kinase anchoring proteins in modulating T-cell activation: progress and future directions. Crit Rev Immunol 26:113–131

    PubMed  CAS  Google Scholar 

  39. Gracie JA, Forsey RJ, Chan WL et al (1999) A proinflammatory role for IL-18 in rheumatoid arthritis. J Clin Invest 104:1393–1401. doi:10.1172/JCI7317

    Article  PubMed  CAS  Google Scholar 

  40. Taskén K, Aandahl EM (2004) Localized effects of cAMP mediated by distinct routes of protein kinase A. Physiol Rev 84:137–167. doi:10.1152/physrev.00021.2003

    Article  PubMed  Google Scholar 

  41. Harris SG, Padilla J, Koumas L et al (2002) Prostaglandins as modulators of immunity. Trends Immunol 23:144–150. doi:10.1016/S1471-4906(01)02154-8

    Article  PubMed  CAS  Google Scholar 

  42. Chen CH, Zhang DH, LaPorte JM et al (2000) Cyclic AMP activates p38 mitogen-activated protein kinase in Th2 cells: phosphorylation of GATA-3 and stimulation of Th2 cytokine gene expression. J Immunol 165:5597–5605

    PubMed  CAS  Google Scholar 

  43. Harizi H, Gualde N (2006) Pivotal role of PGE2 and IL-10 in the cross-regulation of dendritic cell-derived inflammatory mediators. Cell Mol Immunol 3:271–277

    PubMed  CAS  Google Scholar 

  44. Lee JK, Kim SH et al (2004) Differences in signaling pathways by IL-1beta and IL-18. Proc Natl Acad Sci USA 101:8815–8820. doi:10.1073/pnas.0402800101

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Mirko Škoro, MD, PhD, for participation in patient examination. The study was supported by a grant to JMV from the Croatian Ministry of Science, Education and Sports (No. 198-1081874-0183).

Author information

Authors and Affiliations

  1. Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, Dubrava University Hospital, Av. G. Šuška 6, Zagreb, 10040, Croatia

    Jadranka Morovic-Vergles & Melanie Ivana Culo

  2. Department of Pathophysiology, Medical School University of Zagreb, Zagreb, Croatia

    Stjepan Gamulin

  3. Department of Physiology, Medical School University of Zagreb, Zagreb, Croatia

    Filip Culo

Authors
  1. Jadranka Morovic-Vergles
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Melanie Ivana Culo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stjepan Gamulin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Filip Culo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jadranka Morovic-Vergles.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Morovic-Vergles, J., Culo, M.I., Gamulin, S. et al. Cyclic adenosine 5′-monophosphate in synovial fluid of rheumatoid arthritis and osteoarthritis patients. Rheumatol Int 29, 167–171 (2008). https://doi.org/10.1007/s00296-008-0663-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-008-0663-z

Keywords

Search

Navigation