The Effects of One-lung Ventilation on the Production of Endogenous Melatonin and NLRP3 Inflammasome-Related Inflammatory Cytokines in Patients Undergoing Laparoscopic Esophagectomy: A Prospective Randomized Double-Blind Controlled Study

Abstract

Background: NLRP3 inflammasome has been confirmed to play a pivotal role in ventilator-induced lung injury (VILI), while exogenous melatonin can attenuate VILI by inhibiting NLRP3 inflammasome activation in mouse model. However, the relationship between endogenous melatonin and the NLRP3 inflammasome-related inflammatory cytokines in VILI induced by one-lung ventilation (OLV) remains unknown. In this study, we aimed to reveal the relationship between the NLRP3 inflammasome-related inflammatory cytokines: interleukin (IL)-1β, IL-18 and endogenous melatonin in OLV-induced VILI during esophageal cancer surgery.Methods: Twenty-eight patients were randomized to receive “conventional” ventilation (Vt=8 mL/kg) or lung protective ventilation (Vt=5 mL/kg along with 5 cm H 2 O positive end-expiratory pressure (PEEP)). Respiratory variables were evaluated. IL-1β, IL-18 and melatonin in bronchoalveolar lavage fluid (BALF) and plasma were measured.Results: we found that lung protective ventilation during OLV decreased peak airway pressure (Ppeak), plateau airway pressure (Pplat) and driving pressure (ΔP) compared with that in “conventional” ventilation group. Moreover, lung protective ventilation inhibited polymorphonuclear (PMN) cells invasion into BALF. Likewise, lung protective ventilation not only suppressed alveolar and plasma IL-1β secretion, but also reduced increased production of IL-18 in both BALF and plasma after OLV. Furthermore, we found that both alveolar and plasma endogenous melatonin levels in “conventional” ventilation group were lower than that in lung protection group.Conclusion: Taken together, the present study suggested that lung protective ventilation during OLV prevented VILI via suppressing NLRP3 inflammasome-related inflammatory cytokines secretion and restoring the level of endogenous melatonin in patients.Trial registration: the Chinese Clinical Trial Registry, ChiCTR1900026190. Registered 25 September 2019, http://www.chictr.org.cn/edit.aspx?pid=34677&htm=4