Leveraging genetic data to investigate the effects of interleukin-6
receptor signalling on levels of 40 circulating cytokines.
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.