Interleukin 6 regulates psoriasiform inflammation-associated thrombosis

JCI Insight. 2016 Dec 8;1(20):e89384. doi: 10.1172/jci.insight.89384.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calgranulin B / genetics
  • Female
  • Humans
  • Inflammation / complications*
  • Interleukin-23 / antagonists & inhibitors
  • Interleukin-23 / metabolism
  • Interleukin-6 / deficiency
  • Interleukin-6 / metabolism*
  • Keratinocytes
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Psoriasis / pathology*
  • Receptor, TIE-2 / genetics
  • Thrombosis / pathology*


  • Calgranulin B
  • Interleukin-23
  • Interleukin-6
  • Receptor, TIE-2
  • Tek protein, mouse