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Dexmedetomidine alleviates sleep-restriction-mediated exaggeration of postoperative immunosuppression via splenic TFF2 in aged mice.

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.

SUBMITTER: Wang G

PROVIDER: S-EPMC7138555 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Dexmedetomidine alleviates sleep-restriction-mediated exaggeration of postoperative immunosuppression via splenic TFF2 in aged mice.

Wang Guangzhi G Wu Xiaoying X Zhu Guosong G Han Shuangyin S Zhang Jiaqiang J

Aging 20200322 6

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<sup>+</sup> T ce ...[more]

PMID: 32200357

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Project description:Objective: This study was determined to investigate the impact of intranasal dexmedetomidine (DEX) on postoperative sleep quality in older patients (age over 65) with chronic insomnia during their hospitalization after surgery. Design: A randomized double-blind controlled trial was conducted to compare the effects of intranasal dexmedetomidine spray with a placebo group. Setting and Participants: The study was carried out at Xiangya Hospital, Central South University. 110 participants with chronic insomnia were analyzed. Methods: This trial enrolled older patients who underwent total hip/knee arthroplasty and randomized them to receive intranasal dexmedetomidine (2.0 μg/kg) or saline daily at around 9 p.m. after surgery until discharge. The primary outcomes were subjective sleep quality assessed with the Leeds Sleep Evaluation Questionnaire (LSEQ). The secondary outcomes included the objective sleep quality measured with the Acti-graph, the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI). The other outcomes included the incidence of delirium, levels of inflammatory factors, visual analog scale (VAS) pain scores, postoperative opioid consumption, and treatment-related adverse events. Results: 174 patients were screened for eligibility, and 110 were recruited and analyzed. The DEX group had significantly higher scores on both the LSEQ-Getting to sleep and LSEQ-Quality of Sleep at each time point compared to the placebo (p < 0.0001), The least squares (LS) mean difference in LSEQ-GTS score at T0 between placebo group and DEX group was 2 (95% CI, -1-6), p = 0.4071 and at T5 was -14 (95% CI, -17 to -10), p < 0.0001; The LS mean difference in the LSEQ-QOS score at T0 was -1 (95% CI, -4 to 1), p = 0.4821 and at T5 was -16 (95% CI, -21 to -10), p < 0.0001. The DEX group exhibited significant improvement in Total Sleep Time (TST), Sleep Onset Latency (SOL), and Sleep Efficiency (SE), at each time point after treatment compared to the placebo group (p < 0.0001). The PSQI and ISI scores in the DEX group were reduced after treatment (p < 0.001). No significant adverse events were reported with the use of dexmedetomidine. Conclusion and Implications: This study demonstrates that intranasal administration of dexmedetomidine improves postoperative sleep quality in older patients with chronic insomnia who undergo surgery, without increasing the incidence of adverse effects. Clinical Trial Registration: http://www.chictr.org.cn/, identifier ChiCTR2200057133.

Dataset Information

Dexmedetomidine alleviates sleep-restriction-mediated exaggeration of postoperative immunosuppression via splenic TFF2 in aged mice.

Publications

Dexmedetomidine alleviates sleep-restriction-mediated exaggeration of postoperative immunosuppression via splenic TFF2 in aged mice.

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