Transforming growth factor-beta 1 inhibits synthesis of cytokines in endotoxin-stimulated human whole blood
I. Karres, J. P. Kremer, U. Steckholzer, J. S. Kenney and W. Ertel
Division of Trauma Surgery, University Hospital Zurich, Switzerland.
OBJECTIVE: To determine the potency of transforming growth factor-beta
(TGF-beta) for inhibiting proinflammatory cytokine synthesis in
endotoxin-stimulated human whole blood. DESIGN: Endotoxin-stimulated whole
blood from healthy volunteers as an ex vivo model of endotoxemia was
incubated with different concentrations of TGF-beta 1. Cytokine levels in
plasma with a bioassay (for tumor necrosis factor alpha) or an
enzyme-linked immunosorbent assay (for interleukin [IL]-1 beta and IL-6),
messenger RNA (mRNA) expression with northern blotting, and protein levels
with Western blotting were determined. RESULTS: High TGF-beta 1
concentrations (> 100 pg/mL) inhibited (P < .05) secretion of tumor
necrosis factor alpha, IL-1 beta, and IL-6 into
lipopolysaccharide-stimulated whole blood, while low concentrations (<
50 pg/mL) were ineffective. Moreover, TGF-beta 1 inhibited mRNA expression
of tumor necrosis factor alpha and IL-6 in a dose-dependent manner. In
contrast, neither IL-1 beta mRNA expression nor IL-1 beta protein synthesis
were attenuated by TGF-beta 1. CONCLUSION: Transforming growth factor-beta
1, with its downregulatory effect on the synthesis and release of
proinflammatory cytokines by phagocytic cells, represents an inhibitor of
endotoxin-induced inflammatory reactions.
