Skip to main content
Top
Published in: Clinical Rheumatology 12/2017

01-12-2017 | Original Article

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

Authors: Yukio Shimura, Hisashi Kurosawa, Masaru Tsuchiya, Mamiko Sawa, Haruka Kaneko, Lizu Liu, Yuji Makino, Hidetoshi Nojiri, Yoshiyuki Iwase, Kazuo Kaneko, Muneaki Ishijima

Published in: Clinical Rheumatology | Issue 12/2017

Login to get access

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.
Literature
1.
go back to reference Edwards RR, Cahalan C, Mensing G, Smith M, Haythornthwaite JA (2011) Pain, catastrophizing, and depression in the rheumatic diseases. Nat Rev Rheumatol 7:216–224CrossRefPubMed Edwards RR, Cahalan C, Mensing G, Smith M, Haythornthwaite JA (2011) Pain, catastrophizing, and depression in the rheumatic diseases. Nat Rev Rheumatol 7:216–224CrossRefPubMed
2.
go back to reference 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) 63:1543–1549CrossRef 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) 63:1543–1549CrossRef
3.
go back to reference 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 82:814–818CrossRefPubMed 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 82:814–818CrossRefPubMed
4.
go back to reference 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 67:446–457CrossRefPubMed 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 67:446–457CrossRefPubMed
5.
go back to reference Howren MB, Lamkin DM, Suls J (2009) Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med 71:171–186CrossRefPubMed Howren MB, Lamkin DM, Suls J (2009) Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med 71:171–186CrossRefPubMed
6.
go back to reference 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 61:1018–1024CrossRefPubMed 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 61:1018–1024CrossRefPubMed
7.
go back to reference Sellam J, Berenbaum F (2010) The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol 6:625–635CrossRefPubMed Sellam J, Berenbaum F (2010) The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol 6:625–635CrossRefPubMed
9.
go back to reference Scanzello CR (2012) Pathologic and pathogenic processes in osteoarthritis: the effects of synovitis. HSS J 8:20–22CrossRefPubMed Scanzello CR (2012) Pathologic and pathogenic processes in osteoarthritis: the effects of synovitis. HSS J 8:20–22CrossRefPubMed
10.
11.
go back to reference 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 14:77–104CrossRef 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 14:77–104CrossRef
12.
go back to reference 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 75:390–395CrossRefPubMed 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 75:390–395CrossRefPubMed
13.
go back to reference 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 23:1858–1864CrossRefPubMed 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 23:1858–1864CrossRefPubMed
14.
go back to reference 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 21:1179–1184CrossRefPubMed 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 21:1179–1184CrossRefPubMed
15.
go back to reference 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 29:1039–1049CrossRefPubMed 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 29:1039–1049CrossRefPubMed
17.
go back to reference 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 23:1756–1764PubMed 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 23:1756–1764PubMed
18.
go back to reference Moreland JR, Bassett LW, Hanker GJ (1987) Radiographic analysis of the axial alignment of the lower extremity. J Bone Joint Surg Am 69:745–749CrossRefPubMed Moreland JR, Bassett LW, Hanker GJ (1987) Radiographic analysis of the axial alignment of the lower extremity. J Bone Joint Surg Am 69:745–749CrossRefPubMed
19.
go back to reference Colebatch AN, Hart DJ, Zhai G, Williams FM, Spector TD, Arden NK (2009) Effective measurement of knee alignment using AP knee radiographs. Knee 16:42–45CrossRefPubMed Colebatch AN, Hart DJ, Zhai G, Williams FM, Spector TD, Arden NK (2009) Effective measurement of knee alignment using AP knee radiographs. Knee 16:42–45CrossRefPubMed
20.
go back to reference 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 55:306–313CrossRefPubMed 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 55:306–313CrossRefPubMed
22.
go back to reference Chida F, Okayama A, Nishi N, Sakai A (2004) Factor analysis of Zung Scale scores in a Japanese general population. Psychiatry Clin Neurosci 58:420–426CrossRefPubMed Chida F, Okayama A, Nishi N, Sakai A (2004) Factor analysis of Zung Scale scores in a Japanese general population. Psychiatry Clin Neurosci 58:420–426CrossRefPubMed
23.
go back to reference Akai M, Doi T, Fujino K, Iwaya T, Kurosawa H, Nasu T (2005) An outcome measure for Japanese people with knee osteoarthritis. J Rheumatol 32:1524–1532PubMed Akai M, Doi T, Fujino K, Iwaya T, Kurosawa H, Nasu T (2005) An outcome measure for Japanese people with knee osteoarthritis. J Rheumatol 32:1524–1532PubMed
24.
go back to reference 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 60:2037–2045CrossRefPubMedPubMedCentral 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 60:2037–2045CrossRefPubMedPubMedCentral
25.
go back to reference 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 310:1263–1273CrossRefPubMedPubMedCentral 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 310:1263–1273CrossRefPubMedPubMedCentral
26.
go back to reference Daghestani HN, Pieper CF, Kraus VB (2015) Soluble macrophage biomarkers indicate inflammatory phenotypes in patients with knee osteoarthritis. Arthritis Rheum 67:956–965CrossRef Daghestani HN, Pieper CF, Kraus VB (2015) Soluble macrophage biomarkers indicate inflammatory phenotypes in patients with knee osteoarthritis. Arthritis Rheum 67:956–965CrossRef
27.
go back to reference 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 24:1528–1534CrossRefPubMedPubMedCentral 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 24:1528–1534CrossRefPubMedPubMedCentral
28.
go back to reference 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 24:1613–1621CrossRefPubMedPubMedCentral 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 24:1613–1621CrossRefPubMedPubMedCentral
29.
go back to reference 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 60:1009–1014CrossRefPubMed 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 60:1009–1014CrossRefPubMed
30.
go back to reference Edwards RR, Kronfli T, Haythornthwaite JA, Smith MT, McGuire L, Page GG (2008) Association of catastrophizing with interleukin-6 responses to acute pain. Pain 140:135–144CrossRefPubMedPubMedCentral Edwards RR, Kronfli T, Haythornthwaite JA, Smith MT, McGuire L, Page GG (2008) Association of catastrophizing with interleukin-6 responses to acute pain. Pain 140:135–144CrossRefPubMedPubMedCentral
31.
go back to reference 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 29:1185–1190CrossRefPubMed 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 29:1185–1190CrossRefPubMed
32.
go back to reference 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 35:831–838CrossRefPubMed 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 35:831–838CrossRefPubMed
33.
go back to reference 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 36:136–139CrossRefPubMed 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 36:136–139CrossRefPubMed
34.
go back to reference 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 9:46–56CrossRefPubMedPubMedCentral 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 9:46–56CrossRefPubMedPubMedCentral
35.
go back to reference 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 39:413–423CrossRefPubMed 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 39:413–423CrossRefPubMed
36.
go back to reference Lanquillon S, Krieg JC, Bening-Abu-Shach U, Vedder H (2000) Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology 22:370–379CrossRefPubMed Lanquillon S, Krieg JC, Bening-Abu-Shach U, Vedder H (2000) Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology 22:370–379CrossRefPubMed
37.
go back to reference 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 36:155–163CrossRefPubMed 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 36:155–163CrossRefPubMed
38.
go back to reference 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 33:1055–1060CrossRefPubMed 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 33:1055–1060CrossRefPubMed
39.
go back to reference 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 20:473–476CrossRefPubMed 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 20:473–476CrossRefPubMed
40.
go back to reference 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 22:363–388CrossRefPubMed 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 22:363–388CrossRefPubMed
Metadata
Title
Serum interleukin 6 levels are associated with depressive state of the patients with knee osteoarthritis irrespective of disease severity
Authors
Yukio Shimura
Hisashi Kurosawa
Masaru Tsuchiya
Mamiko Sawa
Haruka Kaneko
Lizu Liu
Yuji Makino
Hidetoshi Nojiri
Yoshiyuki Iwase
Kazuo Kaneko
Muneaki Ishijima
Publication date
01-12-2017
Publisher
Springer London
Published in
Clinical Rheumatology / Issue 12/2017
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-017-3826-z

Other articles of this Issue 12/2017

Clinical Rheumatology 12/2017 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.