Abstract: TH-PO0702
Human Splenic Ultrasonography Suppresses Innate Immune Responses to Toll-Like Receptor (TLR) Ligands
Session Information
- AKI: Prevention, Diagnostics, and Management
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 101 AKI: Epidemiology, Risk Factors, and Prevention
Authors
- Nash, William, University of Virginia School of Medicine, Charlottesville, Virginia, United States
- Yao, Junlan, University of Virginia School of Medicine, Charlottesville, Virginia, United States
- Rosner, Mitchell H., University of Virginia School of Medicine, Charlottesville, Virginia, United States
- Hossack, John, University of Virginia School of Medicine, Charlottesville, Virginia, United States
- Okusa, Mark D., University of Virginia School of Medicine, Charlottesville, Virginia, United States
Background
Our prior mouse studies identified spleen-targeted ultrasound (US) as a noninvasive approach to reduce inflammation and protect against AKI through activation of the cholinergic anti-inflammatory pathway (CAP). Studies using US or vagus nerve stimulation demonstrated anti-inflammatory renal protection in murine models of AKI, providing the rationale for an efficacy and dose finding study in healthy human volunteers. Importantly, mice without a spleen or intact splenic nerve signaling failed to exhibit this protection, underscoring the role of the spleen as an immune-regulatory organ within the CAP. Based on these findings, we have selected 4 mechanical index (MI) intensities across the FDA approved range for US application as study “doses” targeting the splenic hilar vasculature in human volunteers.
Methods
Twenty healthy human volunteers between 25 and 50 years-old were enrolled in the study and completed two rounds of US treatment each. The two treatments were at different mechanical intensities (either mechanical index (MI) of 0.6 and 1.4, or 1.0 and 1.8) and were separated by a rest period of at least 14 days. For each US treatment, blood was drawn immediately prior to US application and 24 hours after. The blood was processed into single WBC suspensions via RBC lysis, pelleting, and washing. The WBCs were assessed via flow cytometry for immune cell populations and seeded into 96-well plates for overnight stimulation with TLR ligands. The stimulation supernatants were collected after 18h and cytokine production was analyzed via Luminex. The pre- and post-US results were compared to determine any US-induced change in immune cell populations and cytokine concentrations at each treatment intensity.
Results
We have observed significant or trending reductions in pDC, NK cells, and monocytes in the blood as well as lesser type I and II interferon production after culture for participants treated with the mid-ranges of splenic US treatment (MI 1.0 and 1.4). These effects are most prominent in response to TLR3 and TLR9 ligands, which fits well with the observed immune cell populations impacted.
Conclusion
Our observations indicate that US stimulation of the vasculature at the splenic hilum is capable of impacting innate immune responses by potentially suppressing the abundance and/or inflammatory capacity of populations that are critical players in regulating these first-wave responses, namely pDC, NK, and monocytes.
Acknowledgment
The data for this abstract were generated in part with the services of the University of Virginia Flow Cytometry Core Facility (RRid:SCR_017829) and is partially supported by the NCI Grant (P30-CA044579).
Funding
- NIDDK Support