Delayed neutrophil apoptosis attenuated by melatonin in human acute pancreatitis.
OBJECTIVE
This study evaluated the expression of neutrophil apoptosis and the effects of melatonin at different concentrations on delayed neutrophil apoptosis in different severities of acute pancreatitis in patients.


METHODS
The study population was comprised of 10 patients with severe acute pancreatitis (SAP) and 10 with mild acute pancreatitis (MAP). A total of 10 mL of blood was drawn 24 hours after the onset of the clinical disease for isolation and incubation of the human neutrophils with 4 different concentrations of melatonin. Neutrophil apoptosis activity, CD18 expression, and respiratory burst activity were assessed with flow cytometry 12 hours after incubation. Another group of neutrophils from a healthy control group was used (n = 6) for comparison.


RESULTS
Neutrophil apoptosis in patients with SAP is delayed compared with that of patients with MAP. Neutrophils from patients with SAP or MAP are functionally activated. Melatonin at concentrations of 10(-8), 10(-7), or 10(-6) M reverses the delayed process and enhances apoptosis activity in neutrophils in patients with MAP. Melatonin at concentrations of 10(-7) and 10(-6) M reverses the delayed process and increases apoptosis activity in neutrophils in patients with SAP. Neutrophils from patients with SAP and MAP showed significantly increased CD18 expression and respiratory burst activity. Melatonin at concentrations of 10(-7) or 10(-6) M reverses CD18 expression and respiratory burst activity in neutrophils in patients with SAP.


CONCLUSIONS
This study highlights the importance of neutrophil apoptosis in patients with SAP and raises the possibility of a therapeutic strategy. Study data show that melatonin promotes neutrophil apoptosis in human acute pancreatitis.
Chen
Han-Ming
HM
Department of Surgery, Chang Gung Memorial Hospital, Kwei-Shan, Taoyuan, Taiwan. ming1838@yahoo.com
Hsu
Jun-Te
JT
Chen
Jih-Chang
JC
Ng
Chip-Jin
CJ
Chiu
De-Fa
DF
Chen
Miin-Fu
MF
D000208:Acute Disease; D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D018821:CD18 Antigens / Q000097:blood; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010195:Pancreatitis / Q000097:blood*
D018821:CD18 Antigens; D008550:Melatonin