Serum Levels of Proinflammatory Cytokines in Painful Knee Osteoarthritis and Sensitization

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Abstract

Osteoarthritis (OA) is the most common joint disorder in the world. Among the mechanisms involved in osteoarthritis, biomarkers (cytokines profile) may be related to pain and pain intensity, functional capacity, and pressure pain thresholds (PPT). Thus, the study of these relationships may offer useful information about pathophysiology and associated mechanisms involved in osteoarthritis. Therefore, the objective of this study was to investigate the seric concentration of pro (IL-6, IL-8, and TNF- α) and anti-inflammatory (IL-10) cytokines in patients with painful knee osteoarthritis and to correlate the levels of these biomarkers with the patients' functional capacity and pressure pain threshold (PPT) values.

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Sensitization in patients with painful knee osteoarthritis.

Lars Arendt-Nielsen, Hongling Nie, Mogens B Laursen … (2010)

Pain is the dominant symptom in osteoarthritis (OA) and sensitization may contribute to the pain severity. This study investigated the role of sensitization in patients with painful knee OA by measuring (1) pressure pain thresholds (PPTs); (2) spreading sensitization; (3) temporal summation to repeated pressure pain stimulation; (4) pain responses after intramuscular hypertonic saline; and (5) pressure pain modulation by heterotopic descending noxious inhibitory control (DNIC). Forty-eight patients with different degrees of knee OA and twenty-four age- and sex-matched control subjects participated. The patients were separated into strong/severe (VAS>or=6) and mild/moderate pain (VAS<6) groups. PPTs were measured from the peripatellar region, tibialis anterior (TA) and extensor carpi radialis longus muscles before, during and after DNIC. Temporal summation to pressure was measured at the most painful site in the peripatellar region and over TA. Patients with severely painful OA pain have significantly lower PPT than controls. For all locations (knee, leg, and arm) significantly negative correlations between VAS and PPT were found (more pain, more sensitization). OA patients showed a significant facilitation of temporal summation from both the knee and TA and had significantly less DNIC as compared with controls. No correlations were found between standard radiological findings and clinical/experimental pain parameters. However, patients with lesions in the lateral tibiofemoral knee compartment had higher pain ratings compared with those with intercondylar and medial lesions. This study highlights the importance of central sensitization as an important manifestation in knee OA.

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Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo.

V Mohamed-Ali, S Goodrick, A Rawesh … (1997)

We measured arterio-venous differences in concentrations of tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) across a sc adipose tissue bed in the postabsorptive state in 39 subjects [22 women and 17 men; median age, 36 yr (interquartile range, 26-48 yr); body mass index, 31.8 kg/m2 (range, 22.3- 38.7 kg/m2); percent body fat, 28.7% (range, 17.6-50.7%)]. A subgroup of 8 subjects had arteriovenous differences measured across forearm muscle. Thirty subjects were studied from late morning to early evening; 19 ate a high carbohydrate meal around 1300 h, and 11 continued to fast. We found a greater than 2-fold increase in IL-6 concentrations across the adipose tissue bed [arterial, 2.27 pg/mL (range, 1.42-3.53 pg/mL); venous, 6.71 pg/mL (range, 3.36-9.62 pg/mL); P < 0.001], but not across forearm muscle. Arterial plasma concentrations of IL-6 correlated significantly with body mass index (Spearman's r = 0.48; P < 0.01) and percent body fat (Spearman's r = 0.49; P < 0.01). Subcutaneous adipose tissue IL-6 production increased by the early evening (1800-1900 h) in both subjects who had extended their fasting and those who had eaten. Neither deep forearm nor sc adipose tissue consistently released TNF alpha [across adipose tissue: arterial, 1.83 pg/mL (range, 1.36-2.34 pg/mL); venous, 1.85 pg/mL (range, 1.44-2.53 pg/mL); P = NS: across forearm muscle: arterial, 1.22 pg/mL (range, 0.74-2.76 pg/mL); venous, 0.99 pg/mL (range, 0.69-1.70 pg/mL); P = NS]. Although both IL-6 and TNF alpha are expressed by adipose tissue, our results show that there are important differences in their systemic release. TNF alpha is not released by this sc depot. In contrast, IL-6 is released from the depot and is thereby able to signal systemically.

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Circulating levels of IL-6 and TNF-α are associated with knee radiographic osteoarthritis and knee cartilage loss in older adults.

O Stannus, F Cicuttini, Diane J. Burgess … (2010)

The role of inflammation in osteoarthritis (OA) pathogenesis is unclear, and the associations between inflammatory cytokines and cartilage loss have not been reported. We determined the associations between serum levels of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), knee radiographic OA (ROA) and cartilage loss over 2.9 years in older adults. A total of 172 randomly selected subjects (mean 63 years, range 52-78, 47% female) were studied at baseline and approximately 3 (range 2.6-3.3) years later. IL-6 and TNF-α were assessed by radioimmunoassay. T1-weighted fat-suppressed magnetic resonance imaging of the right knee was performed at baseline and follow-up to determine knee cartilage volume. Knee ROA of both knees was assessed at baseline. At baseline, quartiles of IL-6 and TNF-α were associated with increased prevalence of medial tibiofemoral joint space narrowing (OARSI grade ≥ 1) in multivariate analyses [odds ratio (OR): 1.42 and 1.47 per quartile, respectively, both P<0.05]. Longitudinally, baseline IL-6 predicted loss of both medial and lateral tibial cartilage volume (β: -1.19% and -1.35% per annum per quartile, P<0.05 and P<0.01, respectively), independently of TNF-α. Change in IL-6 was associated with increased loss of medial and lateral tibial cartilage volume (β: -1.18% and -1.06% per annum per quartile, both P<0.05) and change in TNF-α was also negatively associated with change in medial cartilage volume (β: -1.27% per annum per quartile, P<0.05). Serum levels of IL-6 and TNF-α are associated with knee cartilage loss in older people suggesting low level inflammation plays a role in the pathogenesis of knee OA. Copyright © 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

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Journal

Journal ID (nlm-ta): Int J Inflam

Journal ID (iso-abbrev): Int J Inflam

Journal ID (publisher-id): IJI

Title: International Journal of Inflammation

Publisher: Hindawi Publishing Corporation

ISSN (Print): 2090-8040

ISSN (Electronic): 2042-0099

Publication date (Print): 2015

Publication date (Electronic): 2 March 2015

Volume: 2015

Electronic Location Identifier: 329792

Affiliations

¹Clinical Research Center, Institute of Physical Medicine and Rehabilitation, University of São Paulo School of Medicine, Rua Jandiatuba, 580 Vila Andrade, 05716-150 São Paulo, SP, Brazil

²University of São Paulo School of Medicine, Avenida Dr. Arnaldo, 455 Cerqueira César, 01246903 São Paulo, SP, Brazil

³São Paulo Adventist University Center, Estrada de Itapecerica, 5859 Jardim IAE, 05858-001 São Paulo, SP, Brazil

⁴Tropical Hematology Laboratory, Institute of Tropical Medicine of São Paulo and Medical Research Laboratory, LIM 52, University of São Paulo, Avenida Dr. Arnaldo, 455 Cerqueira César, 01246903 São Paulo, SP, Brazil

⁵Institute of Physical Medicine and Rehabilitation, University of São Paulo School of Medicine, Rua Domingo de Soto 100, Vila Mariana, 04116-030 São Paulo, SP, Brazil

⁶Department of Physical Medicine and Rehabilitation, Hacettepe University Medical School, Hacettepe University Faculty of Medicine, Sıhhiye, 06100 Ankara, Turkey

⁷Center for Sensory-Motor Interaction, School of Medicine, Aalborg University, Fredrik Bajers Vej 7, Building D3, 9220 Aalborg E, Denmark

Author notes

*Fábio Marcon Alfieri: fabiomarcon@ 123456bol.com.br

Academic Editor: David A. Hart

Author information

Linamara Rizzo Battistella http://orcid.org/0000-0001-5275-0733

Article

DOI: 10.1155/2015/329792

PMC ID: 4363921

PubMed ID: 25821631

SO-VID: 85b80c79-5a01-45af-9ff4-f6583360b17d

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This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 12 November 2014

Date revision received : 23 December 2014

Date accepted : 23 January 2015

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Serum Levels of Proinflammatory Cytokines in Painful Knee Osteoarthritis and Sensitization

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Most cited references 45

Sensitization in patients with painful knee osteoarthritis.

Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo.

Circulating levels of IL-6 and TNF-α are associated with knee radiographic osteoarthritis and knee cartilage loss in older adults.

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Cited by 35

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