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

被引:92
作者
Spittler, A
Reissner, CM
Oehler, R
Gornikiewicz, A
Gruenberger, T
Manhart, N
Brodowicz, T
Mittlboeck, M
Boltz-Nitulescu, G
Roth, E
机构
[1] Univ Vienna, Dept Surg, Res Labs, AKH, A-1090 Vienna, Austria
[2] Univ Vienna, Inst Gen & Expt Pathol, A-1090 Vienna, Austria
[3] Univ Vienna, Dept Med Comp Sci, A-1090 Vienna, Austria
关键词
sepsis; cytokines; antigen expression; tumor necrosis factor; whole blood cell;
D O I
10.1096/fasebj.13.3.563
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cytokines play a pivotal role in the pathogenesis of septic shock. Proinflammatory cytokines such as tumor necrosis factora-alpha (TNF-alpha) and interleukin-1 eta (IL-1 beta) stimulate the progression of septic shock whereas the anti-inflammatory cytokine ILIO has counterregulative potency. The amino acid glycine (GLY) has been shown to protect against endotoxin shock in the rat by inhibiting TNF-alpha 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-alpha production (P < 0.01) and increased ILIO expression of purified monocytes, Similarly, in a whole blood assay, GLY reduced TNF-alpha (P < 0.0001) and IL-1 beta (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-alpha was augmented by 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 sepsis and in different pathophysiological situations related to hypoxia and reperfusion.
引用
收藏
页码:563 / 571
页数:9
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