Interleukin 6 regulates psoriasiform inflammation–associated thrombosis
Yunmei Wang, … , Thomas S. McCormick, Nicole L. Ward
Yunmei Wang, … , Thomas S. McCormick, Nicole L. Ward
Published December 8, 2016
Citation Information: JCI Insight. 2016;1(20):e89384. https://doi.org/10.1172/jci.insight.89384.
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Research Article Cardiology Dermatology

Interleukin 6 regulates psoriasiform inflammation–associated thrombosis

Abstract

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.

Authors

Yunmei Wang, Jackelyn B. Golden, Yi Fritz, Xiufen Zhang, Doina Diaconu, Maya I. Camhi, Huiyun Gao, Sean M. Dawes, Xianying Xing, Santhi K. Ganesh, Johann E. Gudjonsson, Daniel I. Simon, Thomas S. McCormick, Nicole L. Ward

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Figure 5

Mrp14 and IL-6 deficiency in KC-Tie2 mice and IL-23p19 inhibition in KC-Tie2xMrp14–/– mice have differential effects on blood concentrations of platelets, neutrophils, and monocytes and skin draining lymph node monocyte levels.

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Mrp14 and IL-6 deficiency in KC-Tie2 mice and IL-23p19 inhibition in KC-...
(A) Platelet, (B) neutrophil, and (C) monocyte counts (thousand per microliter) from fresh blood of control (n = 13), KC-Tie2 (n = 11), IL-6–/– (n = 10), KC-Tie2xIL-6–/– (n = 9), Mrp14–/– (n = 10), and KC-Tie2xMrp-14–/– (n = 15) mice. (D) Quantification of CD11b+Ly6Chi monocytes in lymph nodes of KC-Tie2 (n = 19), IL-6–/– (n = 3), KC-Tie2xIL-6–/– (n = 19), KC-Tie2x Mrp14–/– (n = 3), and KC-Tie2x Mrp14–/– mice treated with control IgG (n = 5) or anti–IL-23p19 antibody (n = 9). Values shown represent the mean ± SEM. Dotted line represents archived values of WT control (n = 7). Mrp14–/– animals (n = 3 pooled samples of 3 animals each) had undetectable levels. Each dot represents 1 individual sample. Data were analyzed using a Student’s t test. P values are as indicated.