Skip to main content

Advertisement

Log in

Synovial/Serum leptin ratio in rheumatoid arthritis: the association with activity and erosion

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

Abstract

Reports suggest leptin, which was initially described as a hormone that regulates food intake and energy balance, has an intimate relationship, and interacts with the immune system. Leptin consumption in the synovial cavity in patients with rheumatoid arthritis (RA) reported to have protective effect against erosion. To determine the difference in serum leptin and synovial/serum leptin ratio between RA and control and to assess whether these parameters correlate with systemic inflammation in RA. Also, the hypothesis that synovial/serum leptin ratio could be linked to joint erosion in RA was evaluated. The study subjects consisted of 40 consecutive patients with RA, 30 patients of them had knee effusion, and 30 controls. Ten of these controls had acute knee injury and their synovial fluid was obtained for comparison of synovial/serum leptin ratio with patients with RA. The mean serum leptin in patients with RA was significantly higher than controls. Also, the synovial leptin and synovial/serum leptin ratio in the RA patients with effusion was significantly higher than in the 10 control subjects with traumatic effusion. Serum leptin in the 30 RA patients with effusion was higher than the matched synovial leptin. In RA patients with effusion, synovial/serum leptin ratio was also significantly higher in RA patients with erosion than RA patients without erosion. Serum leptin level and synovial/serum leptin ratio are significantly correlated with the RA duration, DAS28, ESR, CRP, TNF-α, and IL-6. Finally, in regression analysis, only the synovial/serum leptin ratio was positively associated with erosion in patients with RA. In RA, there is a significant increase in circulating leptin levels and synovial/serum leptin ratio compared to non-RA controls. Serum leptin and synovial/serum leptin ratio are significantly in erosive RA than non-erosive RA. Both parameters are correlated with disease duration and parameters of RA activity. In regression analysis, only the synovial/serum leptin ratio was positively associated with erosion in patients with RA. These results indicate that local consumption of leptin in the joint cavity has a protective role against the destructive course of RA.

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. Zwerina J, Redlich K, Schett G, Smolen JS (2005) Pathogenesis of rheumatoid arthritis: targeting cytokines. Ann N Y Acad Sci 10:51716–51729

    Google Scholar 

  2. Faggioni R, Feingold KR, Grunfeld C (2001) Leptin regulation of the immune response and the immunodeficiency of malnutrition. FASEB J 15:2565–2571

    Article  PubMed  CAS  Google Scholar 

  3. Loffreda S, Yang SQ, Lin HZ, Karp CL, Brengman ML, Wang DJ et al (1998) (Leptin regulates proinflammatory immune responses. FASEB J 12:57–65

    PubMed  CAS  Google Scholar 

  4. Baumann H, Morella KK, White DW, Dembski M, Bailon PS, Kim H et al (1996) The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors. Proc Natl Acad Sci USA 93:8374–8378

    Article  PubMed  CAS  Google Scholar 

  5. Gunaydin R, Kaya T, Atay A, Olmez N, Hur A, Koseoglu M (2006) Serum leptin levels in rheumatoid arthritis and relationship with d activity. South Med J 99:1078–1083

    Article  PubMed  Google Scholar 

  6. Bernotiene E, Palmer G, Gabay C (2006) The role of lepin in innate and adaptive immune response. Arthritis Res Ther 8:217–226

    Article  PubMed  Google Scholar 

  7. Wisiowska M, Rok M, Jaszczyk B, Stdpiej K, Cicha M (2007) Serum leptin in rheumatoid arthritis. Rheumatol Int 27:947–954

    Article  Google Scholar 

  8. Fraser DA, Thoen J, Reseland JE, Forre O, Kjeldsen-Kragh J (1999) Decreased CD4 + lymphocyte activation and increased interleukin-4 production in peripheral blood of rheumatoid arthritis patients after acute starvation. Clin Rheumatol 18:394–401

    Article  PubMed  CAS  Google Scholar 

  9. Nishiya K, Nishiyama M, Chang A, Shinto A, Hashimoto K (2002) Serum leptin levels in patients with rheumatoid arthritis are correlated with body mass index. Rinsho Byori 50:524–527

    PubMed  CAS  Google Scholar 

  10. Popa C, Netea MG, Radstake TRDS, van Riel PL, Barrera P, van der Meer JWM (2005) Markers of inflammation are negatively correlated with serum leptin in rheumatoid arthritis. Ann Rheum Dis 64:1195–1199

    Article  PubMed  CAS  Google Scholar 

  11. Hizmetli S, Kisa M, Gokalp N, Bakici MZ (2007) Are plasma and synovial Xuid leptin levels correlated with disease activity in rheumatoid arthritis? Rheumatol Int 27:335–338

    Article  PubMed  CAS  Google Scholar 

  12. Tokarczyk-Knapik A, Nowicki M, Wyromlak J (2002) The relation between plasma leptin concentration and body fat mass in patients with rheumatoid arthritis. Pol Arch Med Wewn 108:761–767

    PubMed  CAS  Google Scholar 

  13. Bokarewa M, Bokarew D, Hultgren O, Tarkowski A (2003) Leptin consumption in the inXamed joints of patients with rheumatoid arthritis. Ann Rheum Dis 62:952–956

    Article  PubMed  CAS  Google Scholar 

  14. Toussirot E, Nguyen NU, Dumoulin G, Aubin F, Cedoz JP, Wendling D (2005) Relationship between growth hormone-IGF-1–IGFBP-3 axis and serum leptin levels with bone mass and body composition in patients with rheumatoid arthritis. Rheumatology (Oxford) 44:120–125

    Article  CAS  Google Scholar 

  15. Salazar-Paramo M, Gonzalez-Ortiz M, Gonzalez-Lopez L, Sanchez-Ortis A, Valera-Gonzalez IC, Martinez-Abundis E, Balcazar-Munoz BR, Garcia-Gonzalez A, Gamez-Nava JI (2001) Serum leptin levels in patients with rheumatoid arthritis. J Clin Rheumatol 7:57–59

    Article  PubMed  CAS  Google Scholar 

  16. Senolt L, Housa D, Vernerová Z, Jirásek T, Svobodová R, Veigl D, Anderlová K, Müller-Ladner U, Pavelka K, Haluzik M (2007) Resistin in rheumatoid arthritis synovial tissue, synovial fluid and serum. Ann Rheum Dis 66:458–463

    Article  PubMed  CAS  Google Scholar 

  17. Targonska-Stepniak B, Majdan M, Dryglewska M (2008) Leptin serum levels in rheumatoid arthritis patients: relation to disease duration and activity. Rheumatol Int 28:585–591

    Article  PubMed  CAS  Google Scholar 

  18. 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 

  19. Prevoo ML, van’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38:44–48

    Article  PubMed  CAS  Google Scholar 

  20. Otero M, Lago R, Gómez R, Lago F, Dieguez C, Gómez-Reino JJ, Gualillo O (2006) Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis. Ann Rheum Dis 65:1198–1201

    Article  PubMed  CAS  Google Scholar 

  21. Seven A, Güzel S, Aslan M, Hamuryudan V (2009) Serum and synovial fluid leptin levels and markers of inflammation in rheumatoid arthritis. Rheumatol Int 29(7):743–747 (Epub 2008 Nov 14)

    Article  PubMed  CAS  Google Scholar 

  22. Gabay C, Dreyer M, Pellegrinelli N, Chicheportiche R, Meier CA (2001) Leptin directly induces the secretion of interleukin 1 receptor antagonist in human monocytes. J Clin Endocrinol Metab 86:783–791

    Article  PubMed  CAS  Google Scholar 

  23. Cohen S, Hurd E, Cush J, Schiff M, Weinblatt ME, Moreland LW et al (2002) Treatment of rheumatoid arthritis with anakinra a recombinant human interleukin-1 receptor antagonist in combination with methotrexate: results of a twenty-four-week multicenter randomized double-blind placebo-controlled trial. Arthritis Rheum; 46:614–624

    Article  PubMed  CAS  Google Scholar 

  24. Maor G, Rochwerger M, Segev Y, Phillip M (2002) Leptin acts as a growth factor on the chondrocytes of skeletal growth centers. J Bone Miner Res 17:1034–1043

    Article  PubMed  CAS  Google Scholar 

  25. Bruun JM, Pedersen SB, Kristensen K, Richelsen B (2002) Effects of pro-inflammatory cytokines and chemokines on leptin production in human adipose tissue in vitro. Mol Cell Endocrinol 190:91–99

    Article  PubMed  CAS  Google Scholar 

  26. Finck BN, Johnson RW (2002) Anti-inflammatory agents inhibit the induction of leptin by tumor necrosis factor-alpha. Am J Physiol Regul Integr Comp Physiol 282:R1429–R1435

    PubMed  CAS  Google Scholar 

  27. Perfetto F, Tarquini R, Simonini G, Bindi G, Mancuso F, Guiducci S, Matucci-Cerinic M, Falcini F (2005) Circulating leptin levels in juvenile idiopathic arthritis: a marker of nutritional status? Ann Rheum Dis 64(1):149–152

    Article  PubMed  CAS  Google Scholar 

  28. Blum WF, Englaro P, Hanitsch S, Juul A, Hertel NT, Müller J, Skakkebaek NE, Heiman ML, Birkett M, Attanasio AM, Kiess W, Rascher W (1997) Plasma Leptin Levels in Healthy Children and Adolescents: Dependence on Body Mass Index, Body Fat Mass, Gender, Pubertal Stage, and Testosterone. Clin Endocrinol Metab 2(9):2904–2910

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shereen M. Olama.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Olama, S.M., Senna, M.K. & Elarman, M. Synovial/Serum leptin ratio in rheumatoid arthritis: the association with activity and erosion. Rheumatol Int 32, 683–690 (2012). https://doi.org/10.1007/s00296-010-1698-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-010-1698-5

Keywords

Navigation