Interleukin 6 regulates psoriasiform inflammation–associated thrombosis
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
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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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 4

IL-6 deficiency prolongs thrombus occlusion formation independent of skin inflammation in KC-Tie2 mice.

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IL-6 deficiency prolongs thrombus occlusion formation independent of ski...
(A) Occlusion times (minutes) following rose bengal–elicited photochemical injury of the carotid artery in control (n = 10), KC-Tie2 (n = 20), IL-6–/– (n = 9), and KC-Tie2xIL-6–/– (n = 13) mice. (B) Representative gross images of the skin phenotype of control, KC-Tie2, IL-6–/–, and KC-Tie2xIL-6–/– mice. (C) Representative images of dorsal skin sections of control, KC-Tie2, IL-6–/–, and KC-Tie2xIL-6–/– mice that were stained using CD11b-specific antibodies. Scale bar: 25 μm. (D) Quantification of epidermal thickness (μm) of dorsal skin sections of control (n = 12), KC-Tie2 (n = 22), IL-6–/– (n = 17), and KC-Tie2xIL-6–/– (n = 13) mice. Values shown represent the mean ± SEM. Each dot represents 1 individual mouse. Data were analyzed using a Student’s t test. P values are as indicated.