Abstract
Major abdominal procedures could induce dysfunction in the immune system and lead to postoperative immunosuppression. Sleep dysfunction is associated with impaired immune activity. However, the effects of postoperative sleep dysfunction on postoperative immune function remain unclear. In this study, we found that sleep-restriction (SR) after surgery increased the spleen weight and the percentage of myeloid-derived suppressor cells (MDSCs) in the spleen, and inhibited splenic CD8+ T cells activity, which was via inhibiting subdiaphragmatic vagus nerve (SVN)-mediated trefoil factor 2 (TFF2) expression in the spleen of aged mice. Dexmedetomidine could alleviate SR-induced these changes via modulating gut microbiota, which acted through SVN. Moreover, we showed essential roles of splenic TFF2 in attenuating SR-induced reduced protective ability against Escherichia coli (E. coli) pneumonia, increased expression of IL-4 and IL-13 in the lung and M2 polarization of alveolar macrophages (AMs), and decreased phagocytic activity of AMs. Dexmedetomidine improved SR-induced reduced protective ability against E. coli pneumonia via splenic TFF2, and subsequently decreasing IL-4 and IL-13 expression in the lung via modulating gut microbiota/SVN, increasing the compromised phagocytic activity of AMs, and ultimately decreasing M2 polarization of AMs. Taken together, dexmedetomidine-induced increase in splenic TFF2 expresssion could alleviate SR-induced exaggeration of postoperative immunosuppression.
Highlights
Major surgery and anaesthesia with severe tissue trauma are strongly associated with extensive immunosuppression in the immediate post-operative period, which arises within a few hours of surgery and lasts for several days, and has been implicated in an increased risk of infectious complications and tumour metastasis formation [1,2,3]
We found that sleep-restriction (SR) after surgery increased the spleen weight and the percentage of myeloid-derived suppressor cells (MDSCs) in the spleen, and inhibited splenic CD8+ T cells activity, which was via inhibiting subdiaphragmatic vagus nerve (SVN)-mediated trefoil factor 2 (TFF2) expression in the spleen of aged mice
We found that sub-diaphragmatic vagotomy (SDV) abrogated dexmedetomidine treatmentmediated decrease in the expression of IL-4 and IL-13 in the lung after SR (P < 0.05 and P < 0.05, respectively; Figure 8H), indicating that gut-microbiota mediated regulation of splenic TFF2 expression via SVN is essential to dexmedetomidine-induced improvement in the antimicrobial activity in E. coli pneumonia
Summary
Major surgery and anaesthesia with severe tissue trauma are strongly associated with extensive immunosuppression in the immediate post-operative period, which arises within a few hours of surgery and lasts for several days, and has been implicated in an increased risk of infectious complications and tumour metastasis formation [1,2,3]. Several studies have demonstrated that patients suffer with poor sleep quality during the first postoperative week [5,6,7,8]. Sleep disruption can activate the sympathetic nervous system (SNS) and the hypothalamic-pituitaryadrenal (HPA) axis and increase evening cortisol levels [11, 12], which could inhibit innate and adaptive immune responses [13,14,15]. In one study including 42 medically and psychiatrically healthy volunteers, acute sleep deprivation resulted in almost a 50% decrease in natural killer cell activity and a 50% decrease in lymphokine killer cell activity [16]. The effects and mechanisms of postoperative sleep disruption on the recovery of immunosuppression remain unclear
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