D1.126 - Therapeutic Splenic Ultrasound Insonation as a Modulator of Pro-atherogenic and Pro-asthmatic Immune Inflammation: A Preclinical Study Design

The spleen is a central but under-evaluated organ in immune regulation, lipid metabolism, and systemic inflammation. Experimental and clinical data suggest that splenic immune pathways are involved in atherosclerosis, allergic inflammation, and autoimmune disorders. Microsplenia and functional splenic impairment have been reported in immune-mediated diseases, including asthma. Recent evidence indicates that targeted splenic ultrasonography may activate anti-inflammatory reflexes and modulate innate and adaptive immune responses. 

Aim was to investigate whether controlled ultrasound insonation of splenic tissue can activate anti-atherogenic and anti-asthmatic immune pathways, leading to downregulation of systemic inflammation and cholesterol-associated immune markers.

A preclinical multimodal design is proposed.

In vitro:Isolated murine splenic macrophages and spleen-derived immune cell cultures will be exposed to diagnostic-range ultrasound insonation using collagen-based scaffold models. Cytokine profiles, macrophage polarization, and immunoglobulin production will be assessed.

In vivo:Mouse/rat models will include:

1. diet-induced atherosclerosis (hypercholesterolemic diet),
2. chronic allergic airway inflammation (including antigen-specific models),
3. autoimmune inflammation models,
4. healthy controls.

Animals will undergo either diagnostic-intensity splenic ultrasound or higher-intensity therapeutic modalities (including ESWT-based protocols). Outcome measures include lipid-associated immune markers, cytokine profiles, macrophage phenotypes, total and antigen-specific Ig levels, and clinical allergy-related outcomes.

Expected Results

Splenic insonation is hypothesized to reduce pro-atherogenic and pro-asthmatic inflammation, normalize cholesterol-associated immune responses, and decrease total and allergen-specific immunoglobulin levels. In allergic models, symptom attenuation is anticipated.

Targeted splenic ultrasound modulation represents a novel, non-pharmacological strategy for influencing immune-lipid interactions and allergic inflammation. This approach may have broad implications for immune-related disorders and supports future Predictive, Preventive, and Personalized Medicine (PPPM)-guided clinical studies in selected allergic and inflammatory phenotypes.