Excitatory and inhibitory amino acid profiles of synovial fluids derived from patients with arthritis

Objective: Rat models of inflammatory synovitis have been shown to contain increased concentrations of excitatory amino acids (EAA). These EAA, glutamate and aspartate have been shown to be excitatory neurotransmitters in the central nervous system. To examine the possibility that increased concentrations of EAA might contribute to the joint's inflammatory response in humans, we analyzed the synovial fluid concentrations of EAAs, and compared them to inhibitory amino acids (IAA), serine and glycine and metabolic control amino acids (CAA), threonine, citrulline, and arginine. Normal AA levels in SF are not available in humans, but are for the rat. Methods: Repository synovial fluid (SF) samples were analyzed by high pressure liquid chromatography (HPLC), and compared to the SF white blood cell count (WBC), and diagnosis. Results: 133 samples with complete chart reviews were analyzed. The most common diagnoses were rheumatoid arthritis, osteoarthritis, and gout EAA and IAA levels did not correlate with WBC count or diagnosis. When compared to normal rat levels, aspartate was 38.95 times normal, glutamic acid 28.95. In contrast, glutamine was 5.69, IAAs glycine 7.62, and serine 6.80, and CAAs threonine 8.23, arginine 7.02, and citrulline 6.13. When EAA mean elevations were compared to IAA and CAA using multiple T-tests, p was less than 0.0001. Conclusion: This data suggests that a neurogenic mechanism of inflammation resulting in EAA elevations may play a role m the synovial inflammatory response, and may be a possible pathway for therapeutic intervention in patients with arthritis.