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Leveraging genetic data to investigate the effects of interleukin-6 receptor signalling on levels of 40 circulating cytokines.
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  • Rezbieara Rahman,
  • Lauren McEwan,
  • David Ryan,
  • Dipender Gill
Rezbieara Rahman
St George's University of London
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Lauren McEwan
St George's University of London
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David Ryan
St George's University Hospitals NHS Foundation Trust
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Dipender Gill
St George's University Hospitals NHS Foundation Trust
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Abstract

Abstract Interleukin 6 (IL-6) is a circulating cytokine that is implicated in a range of inflammatory diseases. However, the broad effects of IL-6 receptor (IL-6R) signalling on other circulating cytokines is not known. Using summary-level data from genome-wide association studies, we leveraged genetic variants that proxy IL-6R signalling in two-sample Mendelian randomization analyses to investigate effects on levels of 40 circulating cytokines. Increased genetically proxied IL-6R signalling was associated with reduced levels of 10 circulating interleukins, chemokines, and growth factors. The findings from this study support feedback effects of IL-6R signalling on reducing levels of a range of circulating cytokines and identify compensatory mechanisms that may be modulating its inflammatory effects. These results provide novel insight into the mechanisms by which IL-6R signalling may be contributing to inflammatory and autoimmune diseases.

Peer review status:ACCEPTED

16 Jun 2021Submitted to British Journal of Clinical Pharmacology
21 Jun 2021Submission Checks Completed
21 Jun 2021Assigned to Editor
23 Jun 2021Reviewer(s) Assigned
09 Aug 2021Review(s) Completed, Editorial Evaluation Pending
10 Aug 2021Editorial Decision: Revise Minor
01 Sep 20211st Revision Received
02 Sep 2021Submission Checks Completed
02 Sep 2021Assigned to Editor
02 Sep 2021Review(s) Completed, Editorial Evaluation Pending
06 Sep 2021Editorial Decision: Accept