Recent studies demonstrated a critical functional connection between the autonomic (sympathetic and parasympathetic) nervous and the immune systems. The carotid sinus nerve (CSN) conveys electrical signals from the chemoreceptors of the carotid bifurcation to the central nervous system where the stimuli are processed to activate sympathetic and parasympathetic efferent signals. Here, we reported that chemoreflex activation via electrical CSN stimulation, in conscious rats, controls the innate immune response to lipopolysaccharide attenuating the plasma levels of inflammatory cytokines such as tumor necrosis factor (TNF), interleukin 1β (IL-1β) and interleukin 6 (IL-6). By contrast, the chemoreflex stimulation increases the plasma levels of anti-inflammatory cytokine interleukin 10 (IL-10). This chemoreflex anti-inflammatory network was abrogated by carotid chemoreceptor denervation and by pharmacological blockade of either sympathetic - propranolol - or parasympathetic - methylatropine – signals. The chemoreflex stimulation as well as the surgical and pharmacological procedures were confirmed by real-time recording of hemodynamic parameters [pulsatile arterial pressure (PAP) and heart rate (HR)]. These results reveal, in conscious animals, a novel mechanism of neuromodulation mediated by the carotid chemoreceptors and involving both the sympathetic and parasympathetic systems.

Our aim was to examine the modulatory effect of electrical activation (EA) of the carotid baroreflex upon the inflammatory responses elicited by LPS. Wistar rats were divided into 3 groups: 1) Control (Saline); 2) LPS; 3) LPS + EA. The subjects were implanted with electrodes around the carotid sinus and catheters into the femoral artery and jugular vein. The surgical procedures were performed under ketamine/xylazine anesthesia. On the next day, the arterial pressure (AP) and heart rate (HR) were recorded, in conscious rats, followed by saline or LPS (1.5 mg/kg iv) administration combined with EA (1mA; 1ms; 30Hz) of the carotid sinus for 1h. Plasma was collected 1, 2 and 3 hs after saline or LPS administration, while the spleen and the heart were collected after 3 hours, to quantify interleukin 6 (IL‐6), 10 (IL‐10), 1β (IL‐1β) and tumor necrosis factor (TNFα). EA did not change the AP or HR, but reduced (LPS vs LPS+EA) inflammatory cytokine TNF‐α (283±139 vs 115±72 pg/µL at the1st h), IL‐6 (11310±1521 vs 3397±709 pg/µL at the 3rd hour) and IL‐1β (296±24 vs 107±29 pg/µL at the1st h), while increased anti‐inflammatory cytokine IL‐10 (25±9 vs 83±25 pg/µL at the 3rd hour). EA reduced IL‐1β (1.66±0.44 vs 1.24±0.14 pg/µg of protein) and increased IL‐10 (0.89±0.08 vs 1.12±0.05 pg/µg of protein) in the spleen, while reduced the IL‐6 (6.43±1 vs 2.88±0.42 pg/µg of protein) and increased IL‐10 (0.8±0.1 vs 1.05±0.14 pg/µg of protein) in the heart. We concluded that electrical activation of the carotid baroreflex, in conscious rats, reduced pro‐inflammatory and increased anti‐inflammatory cytokines, modulating the inflammatory response elicited by LPS.Financial Support: FAPESP, CAPES and CNPq.