Metformin inhibits IL-6 signaling by decreasing IL-6R expression on multiple myeloma cells.

IL-6 signaling plays a crucial role in the pathogenesis of a number of diseases, including multiple myeloma, primary amyloidosis, cytokine release syndrome and other inflammatory conditions. It is central for the growth and survival of malignant plasma cells. IL-6R and IL-6ST receptors transduce IL-6 signaling. Molecular mechanisms regulating expression of IL-6R are not well understood and current therapies are based on monoclonal antibody to target IL-6 signaling. Small molecule inhibitors targeting IL-6 signaling are highly desirable. Metformin specifically decreased IL-6R expression which is mediated via AMPK, mTOR, and miR34a. This is a novel finding and adds to existing therapies targeting IL-6 signaling.