title: 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.affiliation: Division of Cardiovascular Medicine, University Hospitals Cleveland Medical Center and Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Yunmei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Jackelyn B
authors.initials: JB
authors.lastname: Golden
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Fritz
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Xiufen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Doina
authors.initials: D
authors.lastname: Diaconu
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Maya I
authors.initials: MI
authors.lastname: Camhi
authors.affiliation: Division of Cardiovascular Medicine, University Hospitals Cleveland Medical Center and Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Huiyun
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Dawes
authors.affiliation: Department of Dermatology.
authors.forename: Xianying
authors.initials: X
authors.lastname: Xing
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Medicine, and Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Santhi K
authors.initials: SK
authors.lastname: Ganesh
authors.affiliation: Department of Dermatology.
authors.forename: Johann E
authors.initials: JE
authors.lastname: Gudjonsson
authors.affiliation: Division of Cardiovascular Medicine, University Hospitals Cleveland Medical Center and Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Simon
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: McCormick
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Ward
mesh_terms: D000818:Animals; D040502:Calgranulin B / Q000235:genetics; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications*; D053759:Interleukin-23 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015850:Interleukin-6 / Q000172:deficiency / Q000378:metabolism*; D015603:Keratinocytes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011565:Psoriasis / Q000473:pathology*; D042787:Receptor, TIE-2 / Q000235:genetics; D013927:Thrombosis / Q000473:pathology*
chemical_list: D040502:Calgranulin B; D053759:Interleukin-23; D015850:Interleukin-6; D042787:Receptor, TIE-2; C079086:Tek protein, mouse