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Transforming Growth Factor-β1 Inhibits Synthesis of Cytokines in Endotoxin-Stimulated Human Whole Blood

Ina Karres, MD; Jean-Pierre Kremer, PhD; Ursula Steckholzer, MS; John S. Kenney, MA; Wolfgang Ertel, MD
Arch Surg. 1996;131(12):1310-1317. doi:10.1001/archsurg.1996.01430240064008.
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Objective:  To determine the potency of transforming growth factor-β (TGF-β) 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-β1. Cytokine levels in plasma with a bioassay (for tumor necrosis factor α) or an enzyme-linked immunosorbent assay (for interleukin [IL]-1β and IL-6), messenger RNA (mRNA) expression with northern blotting, and protein levels with Western blotting were determined.

Results:  High TGF-β1 concentrations (>100 pg/mL) inhibited (P<.05) secretion of tumor necrosis factor α, IL-1β, and IL-6 into lipopolysaccharide-stimulated whole blood, while low concentrations (<50 pg/mL) were ineffective. Moreover, TGF-β1 inhibited mRNA expression of tumor necrosis factor α and IL-6 in a dose-dependent manner. In contrast, neither IL-1β mRNA expression nor IL-1β protein synthesis were attenuated by TGF-β1.

Conclusion:  Transforming growth factor-β1, with its downregulatory effect on the synthesis and release of proinflammatory cytokines by phagocytic cells, represents an inhibitor of endotoxin-induced inflammatory reactions.Arch Surg. 1996;131:1310-1317


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