Abstract P305: Sympathetic Activation Elicited by Bilateral Carotid Occlusion Attenuates Cytokine Release in Conscious Endotoxemic Rats

Abstract

Our previous studies suggest that carotid occlusion can induce a sympathetic signal able to modulate the immune system. Here, we analyze whether bilateral carotid occlusion (BCO) affect the innate immune response to bacterial lipopolysaccharide (LPS) in endotoxic rats. In order to prevent the neuronal alterations induced by anesthesia, we performed our studies of BCO in conscious rats. Wistar rats were implanted with pneumatic cuffs around the common carotid arteries for BCO. Femoral and peritoneal catheters were also inserted for blood pressure recording and LPS administration. Rats were randomly assigned to the following groups: Saline, LPS + SHAM (LPS in the presence of the occluders but without occlusion) and LPS + BCO (LPS combined with bilateral carotid occlusion). BCO was performed for 20s in conscious awake rats, right before LPS (5.0 mg/kg) or saline (control) administration. Plasma and spleen samples were collected at 90 min after LPS or saline administration. As compared to baseline arterial pressure, BCO produced a peak response in mean arterial pressure of 52 ± 3 mmHg, confirming the sympathetic activation. BCO significantly attenuated TNF-α and IL-1β plasma levels as compared to those in SHAM endotoxemic rats [TNF: 1319 ± 388 (n = 6) vs. 583 ± 138 pg/mL (n = 8), P = 0.03; IL-1β: 2203 ± 256 (n = 5) vs. 1086 ± 157 pg/mL (n = 9), P < 0.001]. BCO also significantly reduced the TNF-α levels in the spleen [5.1 ± 1.3 (n = 7) vs. 1.7 ± 0.4 pg/mg tissue (n = 8), P = 0.005]. By contrast, BCO did not significantly change IL-6 and IL-10 levels in plasma [IL-6: 5609 ± 352 (n = 7) vs. 5879 ± 375 pg/mL (n = 10), P = 0.703; IL-10: 2417 ± 354 (n = 5) vs. 2068 ± 298 pg/mL (n = 9), P = 0.408] or in the spleen [IL-6: 15 ± 3 (n = 7) vs. 14 ± 2 pg/mg tissue (n = 10) P = 0.776; IL-10: 1.6 ± 0.2 (n = 7) vs. 1.3 ± 0.2 pg/mg tissue (n = 9), P = 0.475]. Moreover, the IL-1β level in the spleen was not affected by BCO [54 ± 12 (n = 6) vs. 28 ± 5 pg/mg tissue (n = 9), P = 0.058]. These findings indicate that sympathetic activation by BCO in conscious rats attenuates the pro-inflammatory cytokines release in the endotoxemic model induced by LPS without affecting anti-inflammatory cytokine IL-10.