Low‐Grade Inflammation in Symptomatic Knee Osteoarthritis: Prognostic Value of Inflammatory Plasma Lipids and Peripheral Blood Leukocyte Biomarkers
Open accessAbstract
Objective: Inflammatory mediators, such as prostaglandin E 2 (PGE 2 ) and interleukin‐1β (IL‐1β), are produced by osteoarthritic (OA) joint tissue, where they may contribute to disease pathogenesis. We undertook the present study to examine whether inflammation, evidenced in plasma and peripheral blood leukocytes (PBLs), reflects the presence, progression, or specific symptoms of symptomatic knee OA. Methods: Patients with symptomatic knee OA were enrolled in a 24‐month prospective study of radiographic progression. Standardized knee radiographs were obtained at baseline and 24 months. At baseline, levels of the plasma lipids PGE 2 and 15‐hydroxyeicosatetraenoic acid (15‐HETE) were measured, and transcriptome analysis of PBLs was performed by microarray and quantitative polymerase chain reaction. Results: Baseline PGE 2 synthase (PGES) levels determined by PBL microarray gene expression and plasma PGE 2 levels distinguished patients with symptomatic knee OA from non‐OA controls (area under the receiver operating characteristic curve [AUC] 0.87 and 0.89, respectively, P < 0.0001). Baseline plasma 15‐HETE levels were significantly elevated in patients with symptomatic knee OA versus non‐OA controls ( P < 0.0195). In the 146 patients who completed the 24‐month study, elevated baseline expression of IL‐1β, tumor necrosis factor α, and cyclooxygenase 2 (COX‐2) messenger RNA in PBLs predicted higher risk of radiographic progression as evidenced by joint space narrowing (JSN). In a multivariate model, AUC point estimates of models containing COX‐2 in combination with demographic traits overlapped the confidence interval of the base model in 2 of the 3 JSN outcome measures (JSN >0.0 mm, JSN >0.2 mm, and JSN >0.5 mm; AUC 0.62–0.67). Conclusion: The inflammatory plasma lipid biomarkers PGE 2 and 15‐HETE identify patients with symptomatic knee OA, and the PBL inflammatory transcriptome identifies a subset of patients with symptomatic knee OA who are at increased risk of radiographic progression. These findings may reflect low‐grade inflammation in OA and may be useful as diagnostic and prognostic biomarkers in clinical development of disease‐modifying OA drugs.
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Inflammatory cytokines play pivotal roles in the pathogenesis of degenerative joint disease, orchestrating catabolic processes that lead to progressive cartilage degradation, synovial inflammation, and bone remodeling.
“Inflammatory cytokines play pivotal roles in the pathogenesis of degenerative joint disease, orchestrating catabolic processes that lead to progressive cartilage degradation, synovial inflammation, and bone remodeling [31,32,33].”
From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [32]
The Introduction (page not provided) implicates inflammatory mediators in osteoarthritis and says cytokines and other joint-produced mediators promote cartilage degeneration. The Discussion (page not provided) links synovial inflammation with more severe osteoarthritis. Neither passage establishes that cytokines orchestrate the full catabolic sequence claimed or cause bone remodeling. (LLM, conf=0.85)
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- Authors
- Attur, M., Krasnokutsky, S., Statnikov, A., Samuels, J., Li, Z., Friese, O., Hellio Le Graverand‐Gastineau, M., Rybak, L., Kraus, V. B., Jordan, J. M., Aliferis, C. F., & Abramson, S. B.
- Affiliations
- NYU Langone Health (US)
- Pfizer (United States) (US)
- Pfizer Worldwide Research and Development St. Louis Missouri
- Duke University (US)
- University of North Carolina at Chapel Hill (US)
- ORCID
- Venue
- Arthritis & Rheumatology
- Publisher
- Wiley
- Published
- 2015-10-28
- Volume
- 67
- Issue
- 11
- Pages
- 2905-2915
- ISSN
- 2326-5191 (ISSN-L)
- 2326-5205
- PMC
- PMC4626321
- OpenAlex
- W1870244575
- Cited by
- 120
- References
- 58
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 10 · 2023: 9 · 2022: 11 · 2021: 13 · 2020: 14 · 2019: 18 · 2018: 6 · 2017: 12 · 2016: 9 · 2015: 2
- FWCI
- 8.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Arthritis & Rheumatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (National Library of Medicine) (R01-LM-011179-01A1)
- National Center for Research Resources (1UL1-RR-029893)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-052873)
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Keywords
- knee osteoarthritis, low-grade inflammation, prostaglandin E2, 15-hydroxyeicosatetraenoic acid, peripheral blood leukocytes, inflammatory markers, radiographic progression, joint space narrowing, IL-1β, TNF-α, cyclooxygenase-2, leukocyte transcriptome
- MeSH terms
- Aged, Female, Humans, Hydroxyeicosatetraenoic Acids, Inflammation, Knee Joint, Male, Middle Aged, Prognosis, Prospective Studies, Radiography, Dinoprostone, Biomarkers, Disease Progression, Osteoarthritis, Knee
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