IL-6 potential post-thrombotic syndrome target
MedWire News: US researchers have shown that blocking interleukin (IL)-6 production during venous thrombogenesis may prevent the fibrotic complications associated with post-thrombotic syndrome (PTS).
"It is estimated that a maximum of 60% of patients diagnosed with DVT [deep vein thrombosis] develop PTS, which is characterized by extensive perivenous and mural fibrosis," explain Jose Antonio Diaz (University of Michigan, Ann Arbor) and colleagues.
Current treatment includes elevation of the affected limb, ambulation, and compression stockings, but the success of this regimen varies, and new therapies that target the underlying causes of PTS are needed, say the researchers.
In the present study, Diaz and team investigated whether neutralizing the inflammatory cytokine IL-6 before thrombogenesis decreases vein wall fibrosis, which is caused by vein wall thickening and collagen deposition.
The researchers treated mice with anti-IL-6 antibodies 24 hours before inducing thrombosis via the vena cava ligation model.
Compared with mice pretreated with control immunoglobulin G, those treated with anti-IL-6 antibodies had 28.3% smaller thrombi and 50% lower vein wall C-C motif chemokine ligand 2 (CCL2) gene expression and protein concentration at day 2, and impaired vein wall monocyte recruitment from days 2 to 6.
In addition, intimal thickness was significantly reduced by 44% and vein wall collagen deposition was decreased by 30% at day 14 in the anti-IL-6 group versus the control group.
Analysis of Masson's stained slides from day 14 showed that 35% of the vein wall in the control group was fibrotic compared with 25% in the anti-IL-6 group.
Based on their findings Diaz et al proposed a mechanism for IL-6 induced vein wall fibrosis after DVT.
"During DVT, thrombin activates endothelial cells to express P-selectin... IL-6 is produced by activated venous endothelial cells, which binds to glycoprotein 130 receptors and causes upregulation of vein wall CCL2," they say.
These molecular changes may lead to monocyte recruitment and subsequent secretion of cytokines and growth factors that directly activate fibroblasts and smooth muscle cells, ultimately leading to collagen deposition.
"Collectively, these results clearly demonstrate a link between IL-6 and fibrosis after DVT and suggest that IL-6 inhibition may serve as a new potential target for PTS," conclude the researchers in the Annals of Vascular Surgery.
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By Laura Dean