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Int J Clin Exp Pathol 2013;6(3):492-497

Original Article
Excitatory amino acids display compartmental disparity between plasma and synovial
fluid in clinical arthropathies

Terry A McNearney, Karin N Westlund

Departments of Neuroscience and Cell Biology, Internal Medicine, Microbiology and Immunology, University of Texas Medical Branch,
Galveston, TX; Department of Physiology, University of Kentucky Medical Center, Lexington, KY

Received November 28, 2012; Accepted December 26, 2012; Epub February 15, 2013; Published March 1, 2013

Abstract: Background: Previous studies have demonstrated elevated levels of excitatory amino acids (EAA) glutamate (Glu) and aspartate
(Asp) in the synovial fluid (SF) of patients with active arthritis. The source of SF EAA concentrations are thought in large part to be secondary to
passive diffusion from the plasma across synovial membranes and less so, reflective of local synovial pathology. Objective: This descriptive
report assesses the hypothesis that the SF EAA levels reflect inflammatory processes of the joint and are not dependent on plasma levels.
Methods: Simultaneously drawn plasma and SF samples were obtained from 14 recently deceased cadavers and 10 patients with active
arthritis. Plasma and SF EAA and other amino acid (AA) levels were determined by HPLC. SF: Plasma compartment concentration ratios were
calculated to assess if SF EAA levels were similar to plasma levels. Results: In the cadavers with no antemortem arthritis, the mean SF:
Plasma ratios for Glu and Asp were 4-5-fold lower than the mean ratios seen for 9 other AAs, showing specific discrepancies of EAA levels
between plasma and synovial fluid. In 9 patients with active arthritis, the SF: Plasma concentration ratios were higher in samples derived from
inflammatory arthropathies. Conclusions: Clinical samples demonstrated distinct, independent compartmental EAA concentrations between
blood and joint compartments in support that local arthritic processes rather than plasma influence SF EAA concentrations. The SF EAA levels,
whether from local cell production, local neurogenic sources, and/or transport-gradient mechanisms, parallel local pathology in the joint
compartment and thus serve as surrogate biomarkers of local inflammatory processes. (IJCEP1211037).

Keywords: Glutamate, aspartate, synovial fluid, arthritis, biomarker, neurotransmitter

Address correspondence to:
Dr. Terry A McNearney, Senior Medical Advisor, Neuroscience/Pain, Eli Lilly and Co. Lilly Corporate Center,
anapolis, IN 46240, USA. Office phone: 317-655-0972; Office fax: 317-277-6896; Blackberry: 317-440-1690; E-mail: tmcnearn@utmb.edu