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Thrombosis in Psoriasis Patients: The Connection to IL-6

Psoriasis is a chronic, inflammatory skin disease that causes skin cells to over produce, creating thick patches of scaly skin. It commonly occurs on the scalp, elbows, and knees. While it is known that psoriasis patients are at a greater risk to experience thrombosis[1], researchers are exploring the “why?” A new study[2] may just hold the answer: IL-6.

The study, carried out by Case Western Reserve University’s Department of Dermatology, suggests that the inflammation of the skin in psoriasis patients is linked to their increased risk of developing thrombosis.

Researchers discovered that when IL-6, an interleukin that acts as a pro-inflammatory cytokine, was deleted from mice, thrombosis improved.

“We identify a critical role for elevated skin IL-6 as a regulator of psoriasis-related thrombosis, independent of skin inflammation and demonstrate that improvement in thrombosis corresponds best with decreases in circulating neutrophils and platelets,” states the research article.

See their abstract below:

“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.”

For full details on the study, the article can be found here


[1] Ahlehoff O, Gislason GH, Lindhardsen J, Charlot MG, Jørgensen CH, et al. (2011) Psoriasis Carries an Increased Risk of Venous Thromboembolism: A Danish Nationwide Cohort Study. PLOS ONE 6(3): e18125. doi: 10.1371/journal.pone.0018125

[2] 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. Interleukin 6 regulates psoriasiform inflammation–associated thrombosis. JCI Insight, 2016; 1 (20) DOI: 10.1172/jci.insight.89384

 

 

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