# Synergistic Alleviation of Inflammatory Cytokine Storms in Sepsis Rats by Low‐Intensity Pulsed Ultrasound and Imipenem

**Authors:** Wentao Tang, Juan Deng, Xinyi Zhang, Guolin Song, Juan Qin, Chenghai Li, Xinfang Xiao, Liu Wu, Yilin Tang, Yiqing Zhou, Junfen Li, Sicheng He, Yan Wang

PMC · DOI: 10.1155/mi/7323319 · Mediators of Inflammation · 2026-01-16

## TL;DR

This study shows that combining low-intensity pulsed ultrasound with imipenem reduces inflammation and organ damage in septic rats.

## Contribution

The study introduces a noninvasive combined therapy to mitigate cytokine storms and improve sepsis outcomes.

## Key findings

- LIPUS combined with IMI reduced spleen tissue damage and mitochondrial edema in septic rats.
- The treatment decreased pro-inflammatory cytokines and increased anti-inflammatory IL-10 levels.
- The therapy inhibited the IL-1R/NF-κB pathway, improving survival in septic rats.

## Abstract

This study aimed to investigate the effects of low intensity pulsed ultrasound (LIPUS) combined with imipenem (IMI) on inflammatory responses and organ protection in septic rats.

The study involved 230 Sprague–Dawley (SD) rats, with 80 used for survival analysis and 150 for sampling over 72 h. Histological examination (hematoxylin and eosin [H&E] staining) and transmission electron microscopy (TEM) revealed that LIPUS combined with IMI significantly alleviated spleen tissue damage and reduced mitochondrial edema. Key inflammatory cytokines, such as interleukin‐1 beta (IL‐1β), tumor necrosis factor‐alpha (TNF‐α), and IL‐6 were significantly decreased, while IL‐10 levels increased in the LIPUS + IMI group (p < 0.05). The combined treatment also reduced the expression of cytokines, such as IL‐1 receptor (IL‐1R), nuclear factor kappa B p65 (NF‐κB p65), transforming growth factor‐beta (TGF‐β), and high mobility group protein box 1 (HMGB1), indicating a reduction in inflammation (p < 0.05).

This study presents a novel approach by integrating LIPUS with IMI, providing a noninvasive and effective strategy to mitigate cytokine storms, optimize antibiotic use, and reduce organ damage in sepsis. The protective effects observed are primarily attributed to the inhibition of the IL‐1R/NF‐κB signaling pathway, which significantly improves survival outcomes in septic rats. This combined therapy has potential for enhancing sepsis treatment protocols.

## Linked entities

- **Proteins:** IL1R1 (interleukin 1 receptor type 1), TGFB1 (transforming growth factor beta 1), HMGB1 (high mobility group box 1)
- **Chemicals:** imipenem (PubChem CID 104838)

## Full-text entities

- **Genes:** Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Hmgb1 (high mobility group box 1) [NCBI Gene 25459] {aka Ac2-008, Hmg1}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 59086] {aka Tgfb}, Il10 (interleukin 10) [NCBI Gene 25325] {aka IL10X, If2a}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}
- **Diseases:** Sepsis (MESH:D018805), damage (MESH:D020263), spleen tissue damage (MESH:D013160), mitochondrial edema (MESH:D004487), Inflammatory (MESH:D007249)
- **Chemicals:** IMI (MESH:D015378), H&amp;E (MESH:D006371), eosin (MESH:D004801), hematoxylin (MESH:D006416)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

22 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12809473/full.md

## References

47 references — full list in the complete paper: https://tomesphere.com/paper/PMC12809473/full.md

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Source: https://tomesphere.com/paper/PMC12809473