Title:Sulodexide Down-Regulates the Release of Cytokines, Chemokines, and Leukocyte Colony Stimulating Factors from Human Macrophages: Role of Glycosaminoglycans in Inflammatory Pathways of Chronic Venous Disease
Volume: 12
Issue: 1
Author(s): Ferdinando Mannello, Daniela Ligi, Matteo Canale and Joseph D. Raffetto
Affiliation:
Keywords:
Chronic venous disease, inflammation, glycosaminoglycan, pro-inflammatory cytokines, chemokines, sulodexide,
U-937 macrophage-like cell line.
Abstract: Chronic venous disease (CVeD) is a debilitating condition that affects millions of individuals worldwide. The
condition can result in varicose veins, or advance to severe skin changes and venous ulceration. The fundamental basis for
CVeD is inflammation within the venous circulation and that it is subjected to increased hydrostatic pressure resulting in
increased ambulatory venous pressure. The inflammation involves leukocytes, in particular macrophages and monocytes,
inflammatory modulators and chemokines, cytokine expression, growth factors, metalloproteinase (MMP) activity, and
many regulatory pathways that perpetuate inflammation.
Sulodexide (SDX) is a glycosaminoglycan with pro-fibrinolytic and anti-thrombotic properties. We have previously
demonstrated that SDX inhibits the secretion of pro-zymogen MMP-9 from human leukocytes without displacing high
molecular complexes of MMP-9. The anti-inflammatory properties of SDX on activated leukocytes have not been well
established. We hypothesized that SDX will reduce the secretion of inflammatory mediators from lipopolysaccharide
(LPS)-stimulated macrophages. Therefore, we evaluated the effects of SDX on LPS-stimulated macrophage secretion of
various inflammatory and anti-inflammatory cytokines, chemokines, and colony stimulating factors. We used microplatebased
multiplex immunoassays. LPS-stimulated macrophages in vitro caused a substantial increase of interleukins, tumor
necrosis factor, interferon, chemokines and colony stimulating factors. The addition of SDX caused both a dose-dependent
and dose-independent decrease in nearly all of the inflammatory cytokines, chemokines and colony stimulating factors.
These findings suggest that SDX has a significant effect on the release of inflammatory mediators from macrophages, and
may be useful in the treatment of early and advanced CVeD.
