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

  1. Rachel S. Graham
  2. Daniel P. Zachs
  3. Victoria Cotero
  4. Catherine D’Agostino
  5. Despoina Ntiloudi
  6. Claire R.W. Kaiser
  7. John Graf
  8. Kirk Wallace
  9. Richard Ramdeo
  10. Thomas R. Coleman
  11. Jeffrey Ashe
  12. John Pellerito
  13. Kevin J. Tracey
  14. Bryce A. Binstadt
  15. Sangeeta S. Chavan
  16. Stavros Zanos
  17. Christopher Puleo
  18. Erik Peterson
  19. Hubert H. Lim
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Abstract

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.

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