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

Author:

Graham Rachel S.ORCID,Zachs Daniel P.,Cotero Victoria,D’Agostino Catherine,Ntiloudi Despoina,Kaiser Claire R.W.,Graf John,Wallace Kirk,Ramdeo Richard,Coleman Thomas R.,Ashe Jeffrey,Pellerito John,Tracey Kevin J.,Binstadt Bryce A.,Chavan Sangeeta S.,Zanos Stavros,Puleo Christopher,Peterson Erik,Lim Hubert H.ORCID

Abstract

AbstractHyperinflammation 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.

Publisher

Cold Spring Harbor Laboratory

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