Single exposure to low-intensity pulsed ultrasound has differential effects on circulating pro-inflammatory cytokines in acute versus chronic inflammatory conditions

Aberrant inflammatory responses underlie pathogenicity of most chronic inflammatory conditions including the prototypic autoimmune disease, systemic lupus erythematosus (SLE). Accessible treatment options aimed at reducing inflammation, such as steroids and immunosuppressants, can cause serious side effects and are sometimes inadequate for treating all clinical outcomes in SLE patients. Low-intensity pulsed ultrasound (LIPUS), a non-invasive therapeutic procedure, focused on the spleen and kidneys, has been shown to mitigate the effects of pro-inflammatory cytokines in models of acute kidney injury and inflammation. Our preliminary data suggest that female C57BL/6J mice pre-treated with spleen-kidney LIPUS (20 min/day, intensity=0.1W/cm 2 , pulse repetition rate=100Hz, duty cycle=50%) for five consecutive days before an acute lipopolysaccharide (LPS) challenge, exhibited a significant reduction in plasma pro-inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-6, without affecting tissue cytokines. Meanwhile, a single exposure to 20 minutes of spleen-kidney LIPUS after LPS challenge in C57BL/6J mice significantly reduced plasma IL-6, but not plasma TNF- α or tissue cytokines. Here, we examined the potential therapeutic effects of a single exposure of LIPUS on circulating pro-inflammatory cytokines in the setting of chronic inflammation using the MRL/MpJ-Fas lpr /J mouse model of SLE. Age-matched, 15-week-old female SLE and MRL/MpJ control mice were subjected to spleen-kidney LIPUS for 20 minutes under anesthesia, while sham mice were anesthetized but not exposed. Plasma was harvested two hours post-LIPUS from mice in each group. Plasma TNF-α (pg/mL) was 10-fold higher in SLE sham mice compared to control sham mice (24.5 ± 2.4 vs. 2.3 ± 1.0; p<0.05). A single exposure to LIPUS did not change plasma TNF-α in SLE mice (22.6 ± 3.8) or controls (1.0 ± 0.2). Plasma IL-6 (pg/mL) was not significantly different in SLE and control sham mice (15.7 ± 6.8 vs. 8.2 ± 3.6). A single LIPUS exposure did not alter plasma IL-6 levels in SLE mice (27.1 ± 10.4) or controls (6.2 ± 1.1), which contrasts with a LIPUS-induced decrease in plasma IL-6 levels observed in C57BL/6J mice following an acute inflammatory challenge. Together, these data suggest that a single exposure to LIPUS produces differential effects on modulating circulating cytokines under conditions of either acute or chronic inflammation. We predict a longer LIPUS treatment frequency and/or duration may be required to observe significant reductions in circulating and tissue-specific cytokines in this mouse model of SLE. Studies funded by Department of Defense (LR210096), NIH R01HL153703, and UTSW Startup Funds for KWM This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.