First-in-human demonstration of splenic ultrasound stimulation for non-invasively controlling inflammation

Hyperinflammation and uncontrolled cytokine release in infections and autoimmune diseases require therapy to reduce the innate immune response. Here, we present first in-human data showing reduction in pro-inflammatory cytokine release with ultrasound stimulation of the spleen in healthy subjects and in rheumatoid arthritis patients. Single cell RNA sequencing reveals a decrease in IL-1β and IL-8 transcript levels in circulating monocytes. There is also a down regulation of pathways involved in TNF and IL-6 production, and IFNγ- and NFκB-regulated genes. Additional pre-clinical studies reveal that ultrasound can boost B cell activation and antibody production. Splenic ultrasound offers a new non-invasive therapy for treating hyperinflammation without compromising the adaptive immune response.