First Author | Wang Y | Year | 2016 |
Journal | JCI Insight | Volume | 1 |
Issue | 20 | Pages | e89384 |
PubMed ID | 27942589 | Mgi Jnum | J:290610 |
Mgi Id | MGI:6443584 | Doi | 10.1172/jci.insight.89384 |
Citation | Wang Y, et al. (2016) Interleukin 6 regulates psoriasiform inflammation-associated thrombosis. JCI Insight 1(20):e89384 |
abstractText | Psoriasis patients are at increased risk of heart attack and stroke and have elevated MRP8/14 levels that predict heart attack. The KC-Tie2 psoriasiform mouse model exhibits elevated MRP8/14 and is prothrombotic. Mrp14(-/-) mice, in contrast, are protected from thrombosis, but, surprisingly, KC-Tie2xMrp14(-/-) mice remain prothrombotic. Treating KC-Tie2xMrp14(-/-) mice with anti-IL-23p19 antibodies reversed the skin inflammation, improved thrombosis, and decreased IL-6. In comparison, IL-6 deletion from KC-Tie2 animals improved thrombosis despite sustained skin inflammation, suggesting that thrombosis improvements following IL-23 inhibition occur secondary to IL-6 decreases. Psoriasis patient skin has elevated IL-6 and IL-6 receptor is present in human coronary atheroma, supporting a link between skin and distant vessel disease in patient tissue. Together, these results identify a critical role for skin-derived IL-6 linking skin inflammation with thrombosis, and shows that in the absence of IL-6 the connection between skin inflammation and thrombosis comorbidities is severed. |