Human blood vessels release tumor necrosis factor-α from a smooth muscle cell source

Objectives: In septic shock, the principal source of increased plasma concentrations of tumor necrosis factor alpha (TNF) is considered to be the macrophage. Release from the macrophage is stimulated by bacterial lipopolysaccharide (endotoxin). We tested the hypothesis that vascular tissue also responds to endotoxin by releasing TNF. Design: Prospective repeated measures analysis of timed-release curves. Setting: Anesthesia research laboratory in an academic medical center. Subjects: With institutional Review Board approval and patient consent, segments of internal mammary artery and saphenous vein were obtained during coronary artery bypass surgery. Interventions: None. Measurements and Main Results: Segments of saphenous veins were incubated for 24 hrs in the presence or absence of bacterial lipopolysaccharide. At 0.5, 1, 3, 6, and 24 hrs, medium was assayed for TNF. In other experiments, smooth muscle cells were cultured from saphenous veins, incubated with or without bacterial lipopolysaccharide, and a time-course of TNF release determined. Bacterial lipopolysaccharide (20 μg/mL) significantly stimulated release of TNF from venous tissue in a time- dependent manner. At 0.5 hrs, TNF was undetectable in untreated tissue and was 48 ± 8 U/g wet tissue weight in the presence of bacterial lipopolysaccharide. At 3 hrs, TNF was 43 ± 27 U/g wet tissue weight in untreated and 388 ± 185 U/g wet tissue weight in treated (p < .01 vs. control) tissue. Segments of internal mammary artery responded in a similar manner. In smooth muscle cells cultured from saphenous vein and internal mammary artery, bacterial lipopolysaccharide triggered the release of TNF. At 3 hrs, the release of TNF in control cells was 0.2 ± 0.15 U/mg cell protein and 17 ± 2 U/mg in the presence of 20 μg/mL of bacterial lipopolysaccharide (p < .01 vs. control). Conclusions: Human blood vessels, both artery and vein, produce TNF potentially from a smooth muscle cell source in response to bacterial lipopolysaccharide.