Abstract
Baroreflex and chemoreflex act through the autonomic nervous system, which is involved with the neural regulation of inflammation. The present study reports the effects of reflex physiological sympathetic activation in endotoxemic rats using bilateral carotid occlusion (BCO), a physiological approach involving the baroreflex and chemoreflex mechanisms and the influence of the baroreceptors and peripheral chemoreceptors in the cardiovascular and systemic inflammatory responses. After lipopolysaccharide (LPS) administration, the arterial pressure was recorded during 360 min in unanesthetized rats, and serial blood samples were collected to analyze the plasma cytokine levels. BCO elicited the reflex activation of the sympathetic nervous system, providing the following outcomes: (I) increased the power of the low-frequency band in the spectrum of the systolic arterial pressure during the BCO period; (II) reduced the levels of pro-inflammatory cytokines in plasma, including the tumor necrosis factor (TNF) and the interleukin (IL)-1β; (III) increased the plasma levels of anti-inflammatory cytokine IL-10, 90 min after LPS administration. Moreover, selective baroreceptor or chemoreceptor denervation deactivated mechanosensitive and chemical sensors, respectively, and decreased the release of the LPS-induced cytokine but did not alter the BCO modulatory effects. These results show, for the first time, that physiological reflex activation of the sympathetic circuit decreases the inflammatory response in endotoxemic rats and suggest a novel function for the baroreceptors as immunosensors during the systemic inflammation.
Highlights
The interaction between the central nervous system and the immune system has been studied since the 19th century [1]
bilateral carotid occlusion (BCO) promoted an increase in systolic, diastolic, and mean arterial pressure (Figures 1A–C), in intact animals and in those with selective denervation of baroreceptors (BARO-X) or chemoreceptors (CHEMO-X), indicating an increase in peripheral resistance due to the sympathetic activation
The hypertensive response to BCO was lower in the CHEMO-X than in the intact and BARO-X animals, indicating the importance of the integrity of the chemoreceptors for the peak of hypertensive response during BCO as previously described [26]
Summary
The interaction between the central nervous system and the immune system has been studied since the 19th century [1] Of note, this interaction plays a fundamental role in the regulation of inflammation via activation of neuroendocrine circuits including the hypothalamic–pituitary– adrenal axis [2, 3], the “cholinergic anti-inflammatory pathway” [4, 5], and the “splanchnic antiinflammatory pathway” [6]. Physiological Sympathetic Activation Reduces Inflammation control of the immune system [6,7,8,9,10,11,12] These neuroimmune circuits have been described in endotoxemia, the most known model of inflammation. Through a K+ effluxdependent process, the N-terminal domain of gasdermin D activates NLRP3 inflammasome, which triggers the release of IL1b by active caspase-1, increasing the inflammation [18]
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