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Research Communications |
production and accelerated IL-10 expression
Department of Surgery, Research Laboratories,
a Institute of General and Experimental Pathology,
b Department of Medical Computer Sciences, University of Vienna, A-1090 Vienna, Austria
Cytokines play a pivotal role in the pathogenesis of septic shock.
Proinflammatory cytokines such as tumor necrosis factor-
(TNF-)
and interleukin-1ß (IL-1ß) 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-
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- production
(P<0.01) and increased IL-10 expression of purified
monocytes. Similarly, in a whole blood assay, GLY reduced TNF-
(P<0.0001) and IL-1ß (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- was augmented by
anti-IL-10 antibodies. Furthermore, GLY decreased the amount of IL-1ß
and TNF--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- production and
accelerated IL-10 expression.
1 Correspondence: Department of Surgery, Research Laboratories, AKH, Waehringer Guertel 18-20, A-1090 Vienna, Austria. E-mail: a.spittler{at}akh-wien.ac.at
Key Words: sepsis • cytokines • antigen expression • tumor necrosis factor • whole blood cell
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