Glycine: a new anti-inflammatory immunonutrient

The mechanism of the immunosuppressive effects of glycine and its pathophys iological applications are discussed in this review. Glycine has been well characterized in spinal cord as an inhibitory neurotransmitter which activa tes a glycine-gated chloride channel (GlyR) expressed in postsynaptic membr anes. Activation of the channel allows the influx of chloride, preventing d epolarization of the plasma membrane and the potentiation of excitatory sig nals along the axon. Glycine has recently been shown to have similar inhibi tory effects on several white blood cells, including hepatic and alveolar m acrophages, neutrophils, and lymphocytes. Pharmacological analysis using a GlyR antagonist strychnine, chloride-free buffer, and radio-labeled chlorid e has provided convincing evidence to support the hypothesis that many whit e blood cells contain a glycine-gated chloride channel with properties simi lar to the spinal cord GlyR. Molecular analysis using reverse transcription -polymerase chain reaction and Western blotting has identified the mRNA and protein for the beta subunit of the GlyR in total RNA and purified membran e protein from rat Kupffer cells. Dietary glycine is protective in rat mode ls against endotoxemia, liver ischemia-reperfusion, and liver transplantati on, most likely by inactivating the Kupffer cell via this newly identified glycine-gated chloride channel. Glycine also prevents the growth of B16 mel anomas cell in vivo. Moreover, dietary glycine is protective in the kidney against cyclosporin A toxicity and ischemia-reperfusion injury. Clycine may be useful clinically for the treatment of sepsis, adult respiratory distre ss syndrome, arthritis, and other diseases with an inflammatory component.