Low-concentration Detergent Sclerosants Stimulate White Blood Cells and Release Proinflammatory and Proangiogenic Cytokines in Vitro

J Vasc Surg Venous Lymphat Disord. 2014 Oct;2(4):433-40. doi: 10.1016/j.jvsv.2014.02.005. Epub 2014 May 13.

Abstract

Objective: The objective of this study was to investigate the effects of the detergent sclerosants sodium tetradecyl sulfate (STS) and polidocanol (POL) on the release of proinflammatory and angiogenic mediators from circulating blood cells.

Methods: Whole blood, platelet-rich plasma, platelet-poor plasma, and suspensions of polymorphonuclear cells (PMNCs) and mononuclear cells (MNCs) were incubated with varying concentrations of sclerosants. Enzyme-linked immunosorbent assay was used to detect the release of interferon-γ (IFN-γ); tumor necrosis factor-α (TNF-α); interleukins (IL) 1α, 1β, 6, 8, and 17; vascular endothelial growth factor (VEGF); and basic fibroblast growth factor. Leukocyte activation was assessed by flow cytometry.

Results: IFN-γ and TNF-α were released from STS-stimulated PMNCs at high (387 ng/mL; P < .01) and modest (232 ng/mL; P < .05) quantities, respectively. Both sclerosants induced a weak response in MNCs, releasing minor quantities of IL-1α (STS, 18.2 ng/mL; POL, 14.0 ng/mL), IFN-γ (STS, 41.7 ng/mL; POL, 27.7 ng/mL), and TNF-α (STS, 29.7 ng/mL; POL, 14.0 ng/mL). POL at a wide range of concentrations and in all sample types tested stimulated the release of VEGF, whereas the effect of STS was limited to low concentrations and not detected in MNCs. Both agents stimulated moderate release of IL-8 from PMNCs (STS, 223.3 ng/mL, P < .001; POL, 84.23 ng/mL, P < .05). Neither agent induced a significant rise in basic fibroblast growth factor, IL-6, or IL-17. STS at low concentrations increased the expression of CD11b in both PMNCs and MNCs, suggestive of cellular activation. The activating effect of POL was limited to MNCs.

Conclusions: STS demonstrated proinflammatory activity mediated primarily by IFN-γ released from PMNCs and MNCs. POL had a weak proinflammatory effect limited to MNCs. Both sclerosants (POL > STS) induced a proangiogenic response mediated by VEGF.