Sex-dependent modulation of caerulein-induced acute pancreatitis in C57BL/6J mice

Abstract

Acute pancreatitis (AP) is a life-threatening condition, with a higher mortality rate in men than women and in which estrogens might play a protective role. This study aimed to investigate sex-dependent differences in a mouse model of caerulein-induced AP. Thirty-six C57BL/6J mice (19 females and 17 males) were treated intraperitoneally with phosphate-buffered saline or caerulein, and sacrificed 12 hours, 2 days, or 7 days after the last injection. Blood was collected for amylase, lipase, and glucose determination. Severity and extent of inflammation, apoptosis, and acinar to ductal metaplasia (ADM) in pancreatic tissue were scored histologically and total macrophages, major histocompatibility complex (MHC)-II+ cells, M2 macrophages, T and B cells, neutrophils, apoptosis, and ADM were marked immunohistochemically and quantified by digital image analysis. Serum amylase had a peak at 12 hours, without differences between the sexes. In females, pancreatitis reached a peak at 12 hours with a fast recovery while, in males, the peak was delayed to day 2 with residual apoptosis still present. Macrophages were the main inflammatory cell population, followed by T cells, B cells and neutrophils, without differences between sexes. In males, CD206+ cells and apoptosis were higher at both days 2 and 7, and cytokeratin-19+ (CK19+) ADM was higher at day 7 compared with females. The results of this study revealed a faster onset and resolution of caerulein-induced AP in female mice compared with male mice, supporting a sex-dependent modulation of acute pancreatitis.

Keywords: C57BL/6 mice; caerulein; immunohistochemistry; macrophages; pancreatitis; polarization; sex.