The Carotid Bodies are Required to Activate the Sympathetic Nervous System and Limit TNF-alpha Production During LPS-induced Systemic Inflammation

A growing body of evidence has shown that peripheral systemic inflammation recruits central autonomic circuits that modulate innate immune responses. However, the body-brain pathways governing these neuroimmune interactions remain unclear. Studies indicate that the carotid bodies, a pair of highly perfused sensory organs located at the carotid bifurcations, play a crucial role in these mechanisms. For instance, a recent study demonstrated that the carotid bodies can detect elevated levels of TNF-alpha in the blood to activate central pathways that control splanchnic sympathetic nerve activity which, in turn, limits inflammation. In this study, we investigated whether the carotid bodies are necessary for recruiting the sympathetic nervous system and curbing cytokine synthesis during LPS-induced systemic inflammation, a model in which numerous inflammatory mediators, including TNF-alpha, are elevated in the bloodstream. To address these hypotheses, male Sprague-Dawley Holtzman rats (300 - 385 g) were subjected to SHAM or bilateral carotid body removal (CB-X) surgeries, and systemic inflammation was induced by LPS from E. coli O111:B4 (0.5 mg/kg, i.p.). Measurements were taken 2 hours after LPS or vehicle injection in all experiments. Sympathetic nervous system activation was assessed by c-FOS expression within pre-motor sympathetic neurons in the rostral ventrolateral medulla (RVLM) and recordings of splanchnic sympathetic nerve activity. Systemic LPS activated more RVLM neurons (p<0.05, Student’s t-test) in SHAM (25 ± 5 c-FOS ⁺ cells/section; n = 3 rats) than CB-X rats (14 ± 2 c-FOS ⁺ cells/section; n = 3 rats). Accordingly, the LPS-induced splanchnic sympathoexcitation was greater in SHAM than CB-X rats (n = 2 - 3 rats/group). In separate experiments, we measured plasma TNF-alpha levels using ELISA and found that CB-X rats receiving LPS had significantly higher levels (5680 ± 1186 pg/mL, n = 6) than all other groups (p < 0.05, one-way ANOVA): SHAM + saline (26 ± 23 pg/mL, n = 6), CB-X + saline (120 ± 159 pg/mL, n = 6), and SHAM + LPS (2085 ± 1156 pg/mL, n = 6). In conclusion, the carotid bodies are thus revealed as critical sensors and modulators of the neuroimmune response to LPS-induced acute systemic inflammation, orchestrating sympathetic activation and limiting TNF-alpha production. *Corresponding author at: Department of Physiology and Pathology, School of Dentistry, São Paulo State University, Rua Humaita, 1680, Centro, Araraquara/SP, Brazil – Postal code: 14801-903. E-mail Address: pedro.katayama@unesp.br.

Funding: FAPESP; grants # 2023/07741-8, # 2024/06566-0, and # 2024/08799-2 and PIBIC-RT-UNESP # 16787.

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.