Yang_2022_Evid.Based.Complement.Alternat.Med_2022_8302701

OBJECTIVE: The cholinergic anti-inflammatory pathway (CAP) has been shown to modulate cytokine release by activating alpha-7 nicotinic acetylcholine receptors (alpha7nAChR) in monocytes/macrophages. However, their association with proinflammatory factors and prognosis in patients with acute respiratory distress syndrome (ARDS) has not been clarified. Here, we explored the correlation between CAP activity, proinflammatory factors, and the prognosis of ARDS patients. METHODS: The data of patients with ARDS (n = 65; underwent treatment) and healthy individuals (the control group; n = 65; underwent routine physical examination) at the Chongqing People's Hospital were investigated. Based on the survival status, ARDS patients were divided into a death ARDS group (n = 22) and a survival ARDS group (n = 43), and based on the diagnostic criteria of ARDS, the patients were also divided into a severe ARDS group (n = 30) and a mild-to-moderate ARDS group (n = 35). The levels of acetylcholine (ACh), acetylcholinesterase (AChE), and alpha7nAChR mRNA in peripheral blood monocytes were assessed. The levels of TNF-alpha and IL-6 in peripheral serum and peripheral monocytes were detected by ELISA and Western blot tests. The association between alpha7nAChR and inflammatory factors and prognosis was analyzed. The receiver-operating characteristic (ROC) curve was used to evaluate the reliability of CAP-related factors in predicting the survival status of ARDS patients. RESULTS: Compared with the control group, the levels of ACh, AChE, and alpha7nAChR mRNA of the ARDS group were significantly decreased. And, the ACh, AChE, and alpha7nAChR mRNA levels in the death/severe ARDS group were significantly lower than in the survival/mild-to-moderate ARDS group. However, the levels of TNF-alpha and IL-6 were significantly higher in the severe/death ARDS group. Furthermore, we observed that CAP-related factors were negatively correlated with the levels of IL-6 and TNF-alpha in peripheral serum in the ARDS group. The ROC curve showed that CAP-related factors were reliable markers for predicting the survival status of ARDS patients. CONCLUSION: The related factors of the cholinergic anti-inflammatory pathway were significantly decreased in patients with ARDS, suggesting the ACh, AChE, and alpha7nAChR levels as potential indicators to evaluate the severity and prognosis status of ARDS patients.