Calming the Cytokine Storm - Splenic Ultrasound for Treating Inflammatory Disorders and Potentially COVID-19

Graham, R. S.; Zachs, D. P.; Cotero, V.; DAgostino, C.; Ntiloudi, D.; Kaiser, C. R.; Graf, J.; Wallace, K.; Coleman, T. R.; Ashe, J.; Pellerito, J.; Tracey, K. J.; Binstadt, B.; Chavan, S. S.; Zanos, S.; Puleo, C.; Peterson, E.; Lim, H. H.

Hyperinflammation and uncontrolled cytokine release, which can be seen in severe cases of COVID-19, require therapy to reduce the innate immune response without hindering necessary adaptive immune mechanisms. Here, we show results from the first in-human trials using non-invasive ultrasound stimulation of the spleen to reduce cytokine release in the context of both an acute response in healthy subjects and a chronic inflammatory condition in rheumatoid arthritis patients. Splenic ultrasound results in a reduction in TNF serum levels, as well as IL-1B; and IL-8 transcript levels in monocytes. There is also a down regulation of pathways involved in TNF and IL-6 production, and IFNgamma- and NFKB-regulated genes. Many of these cytokines or pathways are upregulated in COVID-19 patients. There is also a reduction in chemokine transcript levels and other components of the chemotactic response, suggesting that reduction of cellular migration may contribute to the therapeutic effects of ultrasound. There is no inhibition of the adaptive immune response with ultrasound treatment relating to antibody production. This is consistent with a pre-clinical animal model where enhanced antibody production was achieved with splenic ultrasound. Therefore, this new splenic ultrasound approach has the potential to treat acute and chronic hyper-inflammatory diseases, as it lowers cytokine levels without disrupting the normal adaptive immune response. Portable ultrasound technologies are currently being developed and translated to the clinic to treat various inflammatory disorders, with more recent efforts directed towards combatting the hyperinflammation or cytokine storm in COVID-19 patients.