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

Cytokines play a pivotal role in the pathogenesis of septic shock. Proinfla mmatory cytokines such as tumor necrosis factora-alpha (TNF-alpha) and inte rleukin-1 eta (IL-1 beta) stimulate the progression of septic shock whereas the anti-inflammatory cytokine ILIO has counterregulative potency. The ami no acid glycine (GLY) has been shown to protect against endotoxin shock in the rat by inhibiting TNF-alpha production. In the current study we investi gated the role of GLY on lipopolysaccharide (LPS) -induced cell surface mar ker expression, phagocytosis, and cytokine production on purified monocytes from healthy donors. GLY did not modulate the expression of HLA-DR and CD6 4 on monocytes, whereas CD11b/CD18 expression (P < 0.05) and E. coli phagoc ytosis (P < 0.05) decreased significantly. GLY decreased LPS-induced TNF-al pha production (P < 0.01) and increased ILIO expression of purified monocyt es, Similarly, in a whole blood assay, GLY reduced TNF-alpha (P < 0.0001) a nd IL-1 beta (P < 0.0001) synthesis and increased IL-10 expression (P < 0.0 5) in a dose-dependent manner. The inhibitory effects of GLY were neutraliz ed by strychnine, and the production of IL-10 and TNF-alpha was augmented b y anti-IL-10 antibodies. Furthermore, GLY decreased the amount of IL-1 beta and TNF-alpha-specific mRNA. Our data indicate that GLY has a potential to be used as an additional immunomodulatory tool in the early phase of sepsi s and in different pathophysiological situations related to hypoxia and rep erfusion.