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

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.

Elevated inflammatory proteins in cerebrospinal fluid from patients with painful knee osteoarthritis are associated with reduced symptom severity

“…The pro-inflammatory substances, such as cytokines and chemokines, are not only released locally in the joints, they are also released in dorsal root ganglion (DRG) and dorsal horn of the spinal cord by glial cells and nociceptive neurons (Miller et al, 2014). In accordance with this, increased levels of IL-6 and IL-8 in the SF (Monibi et al, 2016;Siqueira et al, 2017;Kosek et al, 2018;Nees et al, 2019) as well as higher concentrations of IL-8, IL-1β and monocyte chemoattractant protein 1 (MCP-1) in the cerebrospinal fluid (CSF) (Lundborg et al, 2010;Kosek et al, 2018) have been documented in knee OA patients. Furthermore, the concentration of MCP-1, a chemokine increasing blood brain barrier (BBB) permeability (Stamatovic et al, 2005;Yao and Tsirka, 2014), was positively correlated across CSF, serum and SF in female OA patients (Kosek et al, 2018) as well as across CSF and serum in patients suffering from disc degenerative disease (Palada et al, 2019), indicating the presence of blood-borne periphery-to-central nervous system (CNS) neuroimmune cross-talk.…”

Serum and synovial fluid concentrations of interleukin-18 and interleukin-20 in patients with osteoarthritis of the knee and their correlation with other markers of inflammation and turnover of joint cartilage

“…The leading symptoms are joint pain, swelling, limited range of motion, and progressive dysfunction leading to reduced physical fitness, social, family, sports, and professional activity. Despite the fact that numerous studies on the aetiopathogenesis of osteoarthritis have been conducted for many years, it has not been possible to determine its full course or all of its metabolic, biochemical, and immunoenzymatic pathways and processes [8][9][10][11][12][13][14][15]. Over many years, numerous substances and markers have been identified which participate in the cascade of inflammation and changes leading to the destruction of cartilage, but this still does not seem to be a complete list [5,6,[16][17][18][19][20][21][22].…”

Biological Potential Alterations of Migratory Chondrogenic Progenitor Cells during Knee Osteoarthritic Progression

“…Notably, mCPCs (grade 3-4) overall exhibited higher inflammatory/catabolic and lower chondroprotective response as evidenced by higher levels of chemokines (CXCL-1, CXCL-6) and lower growth factors (HGF, LAMA5) than mCPCs (grade 1-2). Previous study have suggested innate associations between OA severity and synovial fluid CXCL1 concentration [39] while the upregulation of CXCL-1 and CXCL-6 are also responsible for stronger migration of mCPCs (grade 3-4). Downregulation of HGF may be responsible for decreased chondrogenic performance of mCPCs (grade 3-4) cartilage because study have demonstrated that HGF-rich exosome play a pivotal role in promoting cartilage repair [40].…”