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 3

KC-Tie2xMrp14–/– mice treated with function-blocking antibodies targeting IL-23p19 show significant improvement in skin inflammation, prolonged thrombus occlusion time, and decreases in cutaneous IL-6 protein levels.

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KC-Tie2xMrp14–/– mice treated with function-blocking antibodies targetin...
(A) Representative gross phenotype of KC-Tie2 Mrp14–/– mice following 6 weeks of treatment with IgG or anti–IL-23p19 antibody. (B) H&E-stained dorsal skin sections of KC-Tie2xMrp14–/– mice treated with IgG or anti–IL-23p19 antibody. Scale bar: 25 μm. (C) Quantification of epidermal thickness (μm) of H&E-stained dorsal skin sections of KC-Tie2xMrp14–/– mice treated with IgG (n = 6) or anti–IL-23p19 (p19; n = 9) antibody. (D) Carotid artery occlusion times (minutes) following 6 weeks of treatment with IgG (n = 6) or anti–IL-23p19 (n = 9) antibody. (E) Expression of IL-6 protein (pg/ml), measured using ELISA, in dorsal skin of KC-Tie2xMrp14–/– mice treated with IgG (n = 7) or anti–IL-23p19 (n = 11) antibodies. 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.