New research from the RVC, Galvani Bioelectronics, Queen Mary University of London and Cambridge University has demonstrated how neural connections to the spleen, one of the body’s main lymphoid organs, can be modulated with implanted electrodes to regulate systemic immune responses. This is a significant finding with the potential to improve therapeutic strategies for the treatment of inflammatory conditions in humans.
Acute and chronic inflammatory conditions affect millions of people around the world and while effective molecular therapies are available, many patients do not respond to treatment or become resistant to them over time.
Over the past 20 years, numerous studies have demonstrated an intimate interaction between the nervous and immune systems, which allow the brain to autonomously control and modulate immune response during infection and inflammation. However, this research has been conducted predominantly on rodents which do not provide an anatomically or physiologically relevant model for humans.
Seeking to overcome this challenge, the researchers performed neuroanatomical and functional comparisons of the mouse, rat, pig and human splenic nerve using in vivo and ex vivo preparations, determining that the neural connections to the spleen in pigs were a good model for human splenic nerve innervation.
The group of researchers then used specifically developed techniques for functional electrophysiology to demonstrate that:
- Splenic nerve stimulation parameters could be characterised and optimised using physiological and biological biomarkers, including splenic arterial blood flow and the release of noradrenaline from nerve terminals
- Noradrenaline modulates inflammatory responses of pig splenic leukocytes
- Acute electrical stimulation of the splenic nerve protected pigs from organ failure during severe inflammation
- Acute and chronic stimulation in pigs induced a reduction of pro-inflammatory cell accumulation and pro-inflammatory mediator release and primed the system for a pro-resolutive response during a moderate inflammatory condition.
Additionally, the results showed that the daily splenic nerve neuromodulation via implanted electronics and clinically relevant stimulation parameters was safe and well-tolerated in pigs.
Published in two leading journals, Frontiers in Immunology and Proceedings of the National Academy of Science of the United States of America, the findings of this study show that electrical stimulation of the spleen can stimulate the nervous system to help regulate inflammatory responses as an alternative or adjunct to pharmaceutical therapies.
Professor Dirk Werling, Director of the Center for Vaccinology and Regenerative Medicine at the RVC, said:
“The identification that direct nerve stimulation can impact on the immune response generated opens up a really new and exciting avenue to potentially prevent for example overshooting immune responses under specific conditions.”
Daniel Chew, Director of Translational Research at Galvani Bioelectronics, said:
“Galvani Bioelectronics is developing therapies to treat disease through modulation of neural signals to organs central in chronic disease. These therapies are designed as precision targeted and minimally invasive. These translational efficacy and mechanistic data collected through this very productive academic-industry collaboration, will support the progression of our therapy development for patients suffering chronic inflammatory conditions, transforming patient lives through pioneering precision neuromodulation.”
