Skip to main content

Advertisement

Log in

Serum interleukin 6 levels are associated with depressive state of the patients with knee osteoarthritis irrespective of disease severity

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

Abstract

This cross-sectional study investigated the prevalence of depressive state and association between depressive state and serum interleukin (IL)-6 levels in knee osteoarthritis (OA) patients. A total of 115 painful knee OA patients were enrolled and divided into two groups according to the radiographic OA severity. Pain was evaluated using a visual analog scale (VAS). Depressive state was assessed by the self-rating depression scale (SDS). Serum IL-6 levels were also measured. Pearson’s correlation coefficient was used to assess the correlation between the variants tested, and logistic regression analysis was used to identify factors associated with the depressive state. Fifty-two percent of the patients had an SDS score of ≥ 40, which is indicative of the depressive state. The pain VAS score (r = 0.22, p = 0.02) and serum IL-6 level (r = 0.31, p < 0.01) were independently associated with the SDS score of all early-stage knee OA patients (Kellgren-Lawrence [K/L] grade 2). However, only the serum IL-6 level was independently associated with the SDS scores of advanced-stage knee OA patients (K/L grades 3 and 4, r = 0.36, p < 0.01). A logistic regression analysis revealed that serum IL-6 level was the variable for the SDS score [odds ratio 1.41 (95% confidence interval 1.03–1.94, p < 0.03)]. Approximately half of the knee OA patients were found to be in the depressive state, and their serum IL-6 levels to be associated with the depressive state, irrespective of OA severity.

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.

Similar content being viewed by others

References

  1. Edwards RR, Cahalan C, Mensing G, Smith M, Haythornthwaite JA (2011) Pain, catastrophizing, and depression in the rheumatic diseases. Nat Rev Rheumatol 7:216–224

    Article  CAS  PubMed  Google Scholar 

  2. Murphy SL, Lyden AK, Phillips K, Clauw DJ, Williams DA (2011) Association between pain, radiographic severity, and centrally-mediated symptoms in women with knee osteoarthritis. Arthritis Care Res (Hoboken) 63:1543–1549

    Article  Google Scholar 

  3. Gold SM, Krüger S, Ziegler KJ, Krieger T, Schulz KH, Otte C et al (2011) Endocrine and immune substrates of depressive symptoms and fatigue in multiple sclerosis patients with comorbid major depression. J Neurol Neurosurg Psychiatry 82:814–818

    Article  PubMed  Google Scholar 

  4. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK et al (2010) A meta-analysis of cytokines in major depression. Biol Psychiatry 67:446–457

    Article  CAS  PubMed  Google Scholar 

  5. Howren MB, Lamkin DM, Suls J (2009) Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med 71:171–186

    Article  CAS  PubMed  Google Scholar 

  6. Kojima M, Kojima T, Suzuki S, Oguchi T, Oba M, Tsuchiya H et al (2009) Depression, inflammation, and pain in patients with rheumatoid arthritis. Arthritis Rheum 61:1018–1024

    Article  PubMed  Google Scholar 

  7. Sellam J, Berenbaum F (2010) The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol 6:625–635

    Article  CAS  PubMed  Google Scholar 

  8. Scanzello CR, Goldring SR (2012) The role of synovitis in osteoarthritis pathogenesis. Bone 51:249–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Scanzello CR (2012) Pathologic and pathogenic processes in osteoarthritis: the effects of synovitis. HSS J 8:20–22

    Article  PubMed  Google Scholar 

  10. Mathiessen A, Conaghan PG (2017) Synovitis in osteoarthritis: current understanding with therapeutic implications. Arthritis Res Ther 19:18

    Article  PubMed  PubMed Central  Google Scholar 

  11. Ishijima M, Kaneko H, Hada S, Kinoshita M, Sadatsuki R, Liu L et al (2016) Osteoarthritis as a cause of locomotive syndrome: its influence on functional mobility and activities of daily living. Clin Rev Bone Miner Metab 14:77–104

    Article  Google Scholar 

  12. Atukorala I, Kwoh CK, Guermazi A, Roemer FW, Boudreau RM, Hannon MJ et al (2016) Synovitis in knee osteoarthritis: a precursor of disease? Ann Rheum Dis 75:390–395

    Article  CAS  PubMed  Google Scholar 

  13. Yusup A, Kaneko H, Liu L, Ning L, Sadatsuki R, Hada S et al (2015) Bone marrow lesions, subchondral bone cysts and subchondral bone attrition are associated with histological synovitis in patients with end-stage knee osteoarthritis: a cross-sectional study. Osteoarthr Cartil 23:1858–1864

    Article  CAS  PubMed  Google Scholar 

  14. Shimura Y, Kurosawa H, Sugawara Y, Tsuchiya M, Sawa M, Kaneko H et al (2013) The factors associated with pain severity in patients with knee osteoarthritis vary according to the radiographic disease severity: a cross-sectional study. Osteoarthr Cartil 21:1179–1184

    Article  CAS  PubMed  Google Scholar 

  15. Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K et al (1986) Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum 29:1039–1049

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ravaud P, Giraudeau B, Auleley GR, Chastang C, Poiraudeau S, Ayral X et al (1996) Radiographic assessment of knee osteoarthritis: reproducibility and sensitivity to change. J Rheumatol 23:1756–1764

    CAS  PubMed  Google Scholar 

  18. Moreland JR, Bassett LW, Hanker GJ (1987) Radiographic analysis of the axial alignment of the lower extremity. J Bone Joint Surg Am 69:745–749

    Article  CAS  PubMed  Google Scholar 

  19. Colebatch AN, Hart DJ, Zhai G, Williams FM, Spector TD, Arden NK (2009) Effective measurement of knee alignment using AP knee radiographs. Knee 16:42–45

    Article  PubMed  Google Scholar 

  20. Hinman RS, May RL, Crossley KM (2006) Is there an alternative to the full-leg radiograph for determining knee joint alignment in osteoarthritis? Arthritis Rheum 55:306–313

    Article  PubMed  Google Scholar 

  21. Zung WW (1965) A self-rating depression scale. Arch Gen Psychiatry 12:63–70

    Article  CAS  PubMed  Google Scholar 

  22. Chida F, Okayama A, Nishi N, Sakai A (2004) Factor analysis of Zung Scale scores in a Japanese general population. Psychiatry Clin Neurosci 58:420–426

    Article  PubMed  Google Scholar 

  23. Akai M, Doi T, Fujino K, Iwaya T, Kurosawa H, Nasu T (2005) An outcome measure for Japanese people with knee osteoarthritis. J Rheumatol 32:1524–1532

    PubMed  Google Scholar 

  24. Livshits G, Zhai G, Hart DJ, Kato BS, Wang H, Williams FM et al (2009) Interleukin-6 is a significant predictor of radiographic knee osteoarthritis: the Chingford Study. Arthritis Rheum 60:2037–2045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Messier SP, Mihalko SL, Legault C, Miller GD, Nicklas BJ, DeVita P et al (2013) Effects of intensive diet and exercise on knee joint loads, inflammation, and clinical outcomes among overweight and obese adults with knee osteoarthritis: the IDEA randomized clinical trial. JAMA 310:1263–1273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Daghestani HN, Pieper CF, Kraus VB (2015) Soluble macrophage biomarkers indicate inflammatory phenotypes in patients with knee osteoarthritis. Arthritis Rheum 67:956–965

    Article  CAS  Google Scholar 

  27. Huebner JL, Landerman LR, Somers TJ, Keefe FJ, Guilak F, Blumenthal JA et al (2016) Exploratory secondary analyses of a cognitive-behavioral intervention for knee osteoarthritis demonstrate reduction in biomarkers of adipocyte inflammation. Osteoarthr Cartil 24:1528–1534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kraus VB, McDaniel G, Huebner JL, Stabler TV, Pieper CF, Shipes SW et al (2016) Direct in vivo evidence of activated macrophages in human osteoarthritis. Osteoarthr Cartil 24:1613–1621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Glaser R, Robles TF, Sheridan J, Malarkey WB, Kiecolt-Glaser JK (2003) Mild depressive symptoms are associated with amplified and prolonged inflammatory responses after influenza virus vaccination in older adults. Arch Gen Psychiatry 60:1009–1014

    Article  CAS  PubMed  Google Scholar 

  30. Edwards RR, Kronfli T, Haythornthwaite JA, Smith MT, McGuire L, Page GG (2008) Association of catastrophizing with interleukin-6 responses to acute pain. Pain 140:135–144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Liu L, Ishijima M, Futami I, Kaneko H, Kubota M, Kawasaki T et al (2010) Correlation between synovitis detected on enhanced-magnetic resonance imaging and a histological analysis with a patient-oriented outcome measure for Japanese patients with end-stage knee osteoarthritis receiving joint replacement surgery. Clin Rheumatol 29:1185–1190

    Article  PubMed  Google Scholar 

  32. Ning L, Ishijima M, Kaneko H, Kurihara H, Arikawa-Hirasawa E, Kubota M et al (2011) Correlations between both the expression levels of inflammatory mediators and growth factor in medial perimeniscal synovial tissue and the severity of medial knee osteoarthritis. Int Orthop 35:831–838

    Article  PubMed  Google Scholar 

  33. Doss F, Menard J, Hauschild M, Kreutzer HJ, Mittlmeier T, Müller-Steinhardt M et al (2007) Elevated IL-6 levels in the synovial fluid of osteoarthritis patients stem from plasma cells. Scand J Rheumatol 36:136–139

    Article  CAS  PubMed  Google Scholar 

  34. Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9:46–56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Gimeno D, Kivimäki M, Brunner EJ, Elovainio M, De Vogli R, Steptoe A et al (2009) Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study. Psychol Med 39:413–423

    Article  CAS  PubMed  Google Scholar 

  36. Lanquillon S, Krieg JC, Bening-Abu-Shach U, Vedder H (2000) Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology 22:370–379

    Article  CAS  PubMed  Google Scholar 

  37. Rathbun AM, Yau MS, Shardell M, Stuart EA, Hochberg MC (2017) Depressive symptoms and structural disease progression in knee osteoarthritis: data from the Osteoarthritis Initiative. Clin Rheumatol 36:155–163

    Article  PubMed  Google Scholar 

  38. Traki L, Rostom S, Tahiri L, Bahiri R, Harzy T, Abouqal R et al (2014) Responsiveness of the EuroQol EQ-5D and Hospital Anxiety and Depression Scale (HADS) in rheumatoid arthritis patients receiving tocilizumab. Clin Rheumatol 33:1055–1060

    Article  CAS  PubMed  Google Scholar 

  39. Basterzi AD, Aydemir C, Kisa C, Aksaray S, Tuzer V, Yazici K et al (2005) IL-6 levels decrease with SSRI treatment in patients with major depression. Hum Psychopharmacol 20:473–476

    Article  CAS  PubMed  Google Scholar 

  40. McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-Zeinstra SM et al (2014) OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthr Cartil 22:363–388

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank the members of the outpatient clinic of Department of Orthopedics, Juntendo Tokyo Koto Geriatric Medical Center for data collection.

Funding

This study was supported in part by the High Technology Research Center Grant from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan (to 15K10494 for MI) and the grant from MEXT-Supported Program for the Strategic Research Foundation at Private Universities (2014–2019).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Muneaki Ishijima.

Ethics declarations

This study was conducted with the approval of the ethics committee of Juntendo University. Written informed consent was obtained from each patient prior to inclusion in the study.

Disclosures

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shimura, Y., Kurosawa, H., Tsuchiya, M. et al. Serum interleukin 6 levels are associated with depressive state of the patients with knee osteoarthritis irrespective of disease severity. Clin Rheumatol 36, 2781–2787 (2017). https://doi.org/10.1007/s10067-017-3826-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-017-3826-z

Keywords

Navigation