Splenic Nerve Neuromodulation Reduces Inflammation and Promotes Resolution in Chronically Implanted Pigs.

Area of Science:

• Neuroimmunology
• Translational Medicine
• Surgical Innovation

Background:

• Neuromodulation of the immune system offers a novel therapeutic approach for inflammatory diseases.
• Previous studies demonstrated splenic nerve stimulation's anti-inflammatory effects in anesthetized animals.
• Chronic efficacy and safety testing in a large animal model are crucial for clinical translation.

Purpose of the Study:

• To evaluate the chronic effects and safety of conscious splenic nerve neuromodulation in a large animal model.
• To refine stimulation parameters for efficient splenic nerve activation with minimal cardiovascular impact.
• To assess the immunomodulatory and pro-resolving effects of long-term splenic nerve stimulation.

Main Methods:

• Minimally invasive laparoscopic implantation of a cuff electrode and pulse generator around the splenic neurovascular bundle in pigs.
• Refinement of clinically-relevant stimulation parameters for conscious, freely-behaving animals.
• Assessment of inflammatory markers (TNF-α), monocyte populations, lipid mediators, and nerve integrity post-stimulation.

Main Results:

• Daily splenic nerve neuromodulation was well-tolerated in freely-behaving pigs.
• Significant reduction in circulating tumor necrosis factor alpha and pro-inflammatory monocytes observed.
• Increased concentration of specialized pro-resolving mediators and decreased pro-inflammatory eicosanoids detected.
• Splenic nerve integrity was maintained up to 70 days post-implantation.

Conclusions:

• Chronic splenic nerve neuromodulation using implanted electronics is safe and well-tolerated.
• This therapy effectively modulates the immune system towards a less inflammatory, pro-resolving phenotype.
• These findings support the potential of splenic nerve neuromodulation as a clinical strategy for inflammatory conditions.