To determine the potency of transforming growth factor-β (TGF-β) for inhibiting proinflammatory cytokine synthesis in endotoxin-stimulated human whole blood.
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.
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.
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