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Diagnostic Utility of Cytokine Biomarkers in the Evaluation of Acute Knee Pain

Cuellar, Jason M. MD, PhD; Scuderi, Gaetano J. MD; Cuellar, Vanessa Gabrovsky MD; Golish, S. Raymond MD, PhD; Yeomans, David C. PhD

Journal of Bone & Joint Surgery - American Volume: 01 October 2009 - Volume 91 - Issue 10 - p 2313–2320
doi: 10.2106/JBJS.H.00835
Scientific Articles
Supplementary Content

Background: The diagnosis of clinically important meniscal tears of the knee remains challenging, and it is unknown why only some injuries become painful. The role of inflammatory cytokines in generating pain following meniscal injury remains unclear. This study aimed to investigate the cytokine profile in patients with acute knee pain believed to be secondary to meniscal damage.

Methods: This prospective cohort study included thirty-two patients without rheumatoid arthritis who had knee pain for less than six months, with either an acute or insidious onset, and elected to have arthroscopic treatment after nonoperative management had failed. Twenty-three of these patients elected to have the contralateral, nonoperatively treated knee lavaged at the time of arthroscopy. Fifteen asymptomatic control subjects also contributed samples of knee joint fluid, for a total of seventy samples from forty-seven subjects. Lavage of the operatively treated, contralateral, and control knees was performed with the patient under regional anesthesia prior to arthroscopy, if applicable, by the infusion of sterile saline solution into the knee followed by the immediate withdrawal into a syringe. The concentrations of seventeen inflammatory cytokines and chemokines were measured with use of a multiplexed immunoassay panel. Preoperative magnetic resonance imaging findings and cytokine assay results were compared with intraoperative findings.

Results: Multivariate analysis of variance detected significantly greater concentrations of interferon gamma (IFN-γ); interleukins 2, 4, 6, 10, and 13 (IL-2, IL-4, IL-6, IL-10, and IL-13); monocyte chemotactic protein-1 (MCP-1); and macrophage inflammatory protein-1 beta (MIP-1β) in fluid samples from painful knees than in samples from nonpainful knees. Correlation analysis demonstrated a significant positive correlation between patient-reported pain scores and concentrations of IL-6 (Spearman ρ = 0.7), MCP-1 (ρ = 0.8), MIP-1β (ρ = 0.6), and IFN-γ (ρ = 0.6). These four cytokines also demonstrated a positive correlation with each other (ρ = 0.5 to 0.7). The presence of IFN-γ, IL-6, MCP-1, or MIP-1β performed as well as magnetic resonance imaging in the prediction of intraoperative findings.

Conclusions: Intra-articular concentrations of four inflammatory cytokines IFN-γ, IL-6, MCP-1, and MIP-1β correlated to pain in patients with symptomatic meniscal tears in the knee but were markedly lower in asymptomatic normal knees and in asymptomatic knees with meniscal tears. These cytokines may be involved in the generation of pain following meniscal injury.

1Department of Orthopaedic Surgery, NYU-Hospital for Joint Diseases, 301 East 17th Street, New York, NY 10033

2Department of Orthopaedic Surgery, Stanford University, 450 Broadway, Pavilion C, Redwood City, CA 94063

3Department of Anesthesia, Stanford University, 300 Pasteur Drive, Stanford, CA 94305-5117. E-mail address:

Copyright 2009 by The Journal of Bone and Joint Surgery, Incorporated
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