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. 2019 Aug 29;8(9):1343.
doi: 10.3390/jcm8091343.

Synovial Cytokines Significantly Correlate with Osteoarthritis-Related Knee Pain and Disability: Inflammatory Mediators of Potential Clinical Relevance

Timo A Nees  1 , Nils Rosshirt  1 , Jiji A Zhang  1 , Tobias Reiner  1 , Reza Sorbi  1 , Elena Tripel  1 , Tilman Walker  1 , Marcus Schiltenwolf  1 , Sébastien Hagmann  1 , Babak Moradi  2
Affiliations

Synovial Cytokines Significantly Correlate with Osteoarthritis-Related Knee Pain and Disability: Inflammatory Mediators of Potential Clinical Relevance

Timo A Nees et al. J Clin Med. .

Abstract

The aim of this study was to identify inflammatory mediators of potential clinical relevance in synovial fluid (SF) samples of patients with knee osteoarthritis (OA). Therefore, radiographic OA severity, knee pain and function of 34 OA patients undergoing unicompartmental (UC) and bicompartmental (BC) knee arthroplasty were assessed prior to surgery and SF samples were analyzed for a broad variety of inflammatory mediators, including interleukins (ILs), interferons (IFNs), C-X-C motif ligand chemokines (CXCLs), and growth factors (nerve growth factor; NGF, vascular endothelial growth factor; VEGF, and stem cell growth factor β; SCGF-β) using multiplex assay. Significant differences were observed between the SF levels of different inflammatory markers. When compared to UC OA, significantly higher concentrations of IL-7, IL-8, IL-10, IL-12, IL-13, IFN-γ, VEGF and CXCL1 were detected in BC OA. Correlation analyses revealed significant associations between OA severity and IL-6, IL-8, IFN-γ, SCGF-β, VEGF, CXCL1. Interestingly, increases in both anti- (IL-10, IL-13) and pro-inflammatory (IL-7, IL-12, IFN-γ) cytokines, as well as growth factors (SCGF-β, VEGF), correlated significantly with the level of knee pain. Poorer knee function was associated with higher IL-6, IL-10, IL-12, IL-13, IL-18, βNGF, SCGF-β, VEGF and CXCL9 levels. In conclusion, this study provides an extensive profile of synovial inflammatory mediators in knee OA and identifies cytokines of potential clinical relevance. In fact, five of the mediators examined (IL-10, IL-12, IL-13, SCGF-β, VEGF) significantly correlate with both knee pain and function.

Keywords: cytokines; inflammation; osteoarthritis; pain; synovial fluid.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Clinical parameters of the study population. Mean (± SD) K&L, NRS and OKS-12 scores of the total study population (Total) and the patients diagnosed with UC or BC OA are presented. Comparing UC OA with BC OA no significant differences in (A) the severity of OA (K&L score), (B) knee pain (NRS) and (C) function (OKS-12) were observed. Unpaired student’s t-test was used for statistical analysis. Data are expressed as mean ± SD.
Figure 2
Figure 2
Cytokine pattern in synovial fluid (SF) of patients with knee osteoarthritis. The Pro-Human Cytokine Multiplex Assay (Bio-Rad) was used to analyze the cytokines in SF samples. Cytokine and chemokine concentrations were calculated by reference to the standard curve. The sensitivity of the multiplex kit was < 5 pg/mL. Data are presented as box and whisker plot showing median (interquartile range; IQR) values (box) and minimum to maximal values (whiskers).
Figure 3
Figure 3
Significant correlations between inflammatory mediators and clinical parameters (NRS, OKS). Correlation analyses were performed using Spearman’s rank correlation coefficient (r). Since IL-10, IL-12, IL-13, SCGFβ and VEGF did not show Gaussian distribution Mann–Whitney U test was performed to calculate differences in SF cytokine concentrations between unicompartmental (UC) and bicompartmental (BC) osteoarthritis. p-Values < 0.05 were considered statistically significant and are indicated with asterisks: * p < 0.05; ** p < 0.01. SF = synovial fluid; NRS = numerical rating scale; OKS = Oxford Knee Score; IL = interleukin; SCGF = stem cell growth factor; VEGF = vascular endothelial growth factor.
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