Search

Melatonin is a chronobiotic hormone, which can regulate human diseases like cancer, atherosclerosis, respiratory disorders, and microbial infections by regulating redox system. Melatonin exhibits innate immunomodulation by communicating with immune system and influencing neutrophils to fight infections and inflammation. However, sustaining redox homeostasis and reactive oxygen species (ROS) generation in neutrophils are critical during chemotaxis, oxidative burst, phagocytosis, and neutrophil extracellular trap (NET) formation. Therefore, endogenous antioxidant glutathione (GSH) redox cycle is highly vital in regulating neutrophil functions. Reduced intracellular GSH levels and glutathione reductase (GR) activity in the neutrophils during clinical conditions like autoimmune disorders, neurological disorders, diabetes, and microbial infections lead to dysfunctional neutrophils. Therefore, we hypothesized that redox modulators like melatonin can protect neutrophil health and functions under GSH and GR activity–deficient conditions. We demonstrate the dual role of melatonin, wherein it protects neutrophils from oxidative stress‐induced apoptosis by reducing ROS generation; in contrast, it restores neutrophil functions like phagocytosis, degranulation, and NETosis in GSH and GR activity–deficient neutrophils by regulating ROS levels both in vitro and in vivo. Melatonin mitigates LPS‐induced neutrophil dysfunctions by rejuvenating GSH redox system, specifically GR activity by acting as a parallel redox system. Our results indicate that melatonin could be a potential auxiliary therapy to treat immune dysfunction and microbial infections, including virus, under chronic disease conditions by restoring neutrophil functions. Further, melatonin could be a promising immune system booster to fight unprecedented pandemics like the current COVID‐19. However, further studies are indispensable to address the clinical usage of melatonin. [ABSTRACT FROM AUTHOR]

Delayed neutrophil apoptosis has been implicated as the mechanism of the systemic inflammatory response. Herein, we examined the effect of melatonin on the neutrophil apoptosis in ischemia and reperfusion of the human liver. We studied seven patients receiving elective hepatectomy for liver tumor and ten patients receiving laparoscopic cholecystectomy for gallstones. Ten milli liters of blood was drawn isolation and incubation of the human neutrophils. Neutrophil apoptosis activity and CD18 expression and respiratory burst activity were assessed flow cytometrically. Another group of neutrophils included those from the patients receiving hepatectomy and isolated and incubated with melatonin. Neutrophil apoptosis is delayed from patients after hepatectomy or laparoscopic cholecystectomy when compared with that of the preoperative state. The decrease in the apoptosis activity is more severe in patients receiving hepatectomy as compared with those receiving laparoscopic cholecystectomy. Neutrophils from patients receiving hepatectomy or laparoscopic cholecystectomy are functionally activated. Melatonin can reverse the delayed process and enhance the apoptosis activity in neutrophils from patients receiving hepatectomy. This study demonstrates that melatonin enhances neutrophil apoptosis in patients receiving hepatectomy involving ischemia and reperfusion of the human liver. [ABSTRACT FROM AUTHOR]