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Immunomodulatory effects of glycine on LPS‐treated monocytes: reduced TNF‐α production and accelerated IL‐10 expression

Cytokines play a pivotal role in the pathogenesis of septic shock. Proinflammatory cytokines such as tumor necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) stimulate the progression of septic shock whereas the anti‐inflammatory cytokine IL‐10 has counterregulative potency. The amino acid glycine (GLY) has been shown to protect against endotoxin shock in the rat by inhibiting TNF‐α production. In the current study we investigated the role of GLY on lipopolysaccharide (LPS) ‐induced cell surface marker expression, phagocytosis, and cytokine production on purified monocytes from healthy donors. GLY did not modulate the expression of HLA‐DR and CD64 on monocytes, whereas CD11b/CD18 expression (P<0.05) and E. coli phagocytosis (P<0.05) decreased significantly. GLY decreased LPS‐induced TNF‐α production (P<0.01) and increased IL‐10 expression of purified monocytes. Similarly, in a whole blood assay, GLY reduced TNF‐α (P< 0.0001) and IL‐1β (P<0.0001) synthesis and increased IL‐10 expression (P<0.05) in a dose‐dependent manner. The inhibitory effects of GLY were neutralized by strychnine, and the production of IL‐10 and TNF‐α was augmented by anti‐IL‐10 antibodies. Furthermore, GLY decreased the amount of IL‐1β and TNF‐α‐specific mRNA. Our data indicate that GLY has a potential to be used as an additional immunomodulatory tool in the early phase of sepsis and in different pathophysiological situations related to hypoxia and reperfusion.—Spittler, A., Reissner, C. M., Oehler, R., Gornikiewicz, A., Gruenberger, T., Manhart, N., Brodowicz, T., Mittlboeck, M., Boltz‐Nitulescu, G., Roth, E. Immunomodulatory effects of glycine on LPS‐treated monocytes: reduced TNF‐α production and accelerated IL‐10 expression. FASEB J. 13, 563–571 (1999)