Abstract 13985: Anti-inflammatory Cytokine Interleukin-35 Inhibits Lipopolysaccharide-induced Vascular Inflammation
Interleukin-35 (IL-35), consisting of two subunits, Epstein-Barr virus-induced gene 3 (EBI3) and p35, is a novel anti-inflammatory responsive cytokine in IL-12 cytokine family. IL-35 is produced by CD4+CD25+ regulatory T cells (Tregs). Although it has been shown that IL-35 suppresses the development of chronic inflammatory diseases such as asthma and inflammatory bowel disease through inhibiting CD4+ T cell proliferation in mouse, the issue of how IL-35 inhibits acute inflammation remained unknown. Vascular endothelial cell activation is the initial step of vascular inflammatory response to acute and chronic pathological stimuli. Using lipopolysaccharide (LPS)-induced mouse endotoxemia model, we observed that IL-35 significantly inhibited endothelial cell activation in aorta and different sizes of vessels in lung and cremaster muscle using histochemical method and intravital microscopy technique. Mechanistically, we found that both new identified IL-35 dimeric receptors gp130 and IL-12Rβ2 were detected in human primary endothelial cells. IL-35 inhibited LPS-induced upregulation of adhesion molecule vascular cell adhesion molecule 1 (VCAM-1) in human aortic endothelial cells, a marker of endothelial activation. Interestingly, we observed IL-35 also downregulated acute inflammatory related cytokine levels in mice suffering from endotoxemia. These results suggest that novel suppressive cytokine IL-35 protects tissues from inflammatory response via two pathways, direct inhibition of endothelial activation and indirect inhibition of other proinflammatory cytokine-induced inflammation acceleration. Our data provide an important insight for future immunological therapy for vascular inflammation and other inflammatory diseases.
- © 2013 by American Heart Association, Inc.