Exercise Intensities Modulates Inflammatory Gene Expression to Minced Muscle Repair Following Volumetric Muscle Loss

Volumetric muscle loss (VML) causes structural and functional damage beyond the muscle’s regenerative capacity, leading to chronic inflammation and incomplete recovery. Although treatments such as autologous muscle repair offer some benefits, they still fail to fully restore muscle structure and function. Chronic exercise training as an adjunct therapeutic approach modulates inflammatory signaling. Moreover, exercise training intensity influences immune and cytokine activity after minor injury, leading to different recovery patterns. Although lower-intensity exercise reduced pro-inflammatory activation, its impact on inflammation following minced muscle grafts (MMG) in a VML model is unknown. Therefore, this study aimed to determine whether exercise intensity modulates pro-inflammatory cytokine responses following MMG repair in a rat VML model. We hypothesized that low intensity exercise would reduce inflammatory signaling more than high intensity exercise. To test this, we used 32 adults Sprague Dawley rats 16 males, and 16 females) with surgically induced VML in the left tibialis anterior (LTA) where ~20% of the muscle was excised, minced and replaced as an autologous MMG repair. The right TA (RTA) served as contralateral control. One week after VML and MMG repair, animals were assigned to low intensity (15m/min for 45 minutes) or a high intensity (25-30 m/min for 15 minutes) exercise group for 11 weeks (5 days/week). TA muscles were excised to determine the mRNA expression abundance of pro-inflammatory cytokines, including Tnf-α, Il-6, and Il-1β, using qRT- PCR. Two-way ANOVA assessed interactions of exercise intensity (low vs. high) and injury (LTA vs. RTA) on mRNA abundance, with significance at p 0.05). In males, Tnf-α mRNA abundance in the LTA was approximately120% lower in the high intensity group compared with the low intensity group (p = 0.0022). In the low intensity group, males showed an approximately 3-fold higher Il-6 mRNA abundance in the LTA (injured) compared to the RTA (uninjured) (p 0.05). However, in males, Il-6 mRNA abundance in the LTA was approximately 120% lower in the high intensity group compared with the low intensity group (p < 0.01). In contrast, Il-1β did not differ significantly between exercise intensities or injury conditions in either sex. Our findings suggest exercise intensity differentially influences inflammatory pathways after MMG repair, and low intensity exercise may be ineffective for VML, particularly in males. This abstract was presented at the American Physiology Summit 2026 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.