Interleukin 6 regulates psoriasiform inflammation-associated thrombosis.
basic_science · Level V
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- Record sourced from PubMed, PMID 27942589.
- Also identified by DOI 10.1172/jci.insight.89384 and PMC identifier 5135273.
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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. <i>Mrp14</i><sup>-/-</sup> mice, in contrast, are protected from thrombosis, but, surprisingly, KC-Tie2x<i>Mrp14</i><sup>-/-</sup> mice remain prothrombotic. Treating KC-Tie2x<i>Mrp14</i><sup>-/-</sup> 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.
Medical subject headings
- Inflammation
- Interleukin-6
- Psoriasis
- Thrombosis