Published online Dec 7, 2018. doi: 10.3748/wjg.v24.i45.5131
Peer-review started: September 27, 2018
First decision: October 14, 2018
Revised: October 20, 2018
Accepted: November 9, 2018
Article in press: November 9, 2018
Published online: December 7, 2018
Severe acute pancreatitis (SAP) is a highly lethal disease with limited therapeutic options and is characterized by a critical systemic inflammatory response. Pancreatitis-associated ascitic fluids (PAAF) play an important role in the pathogenesis of SAP because of the pro-inflammatory mediators the PAAF contain. Our previous studies suggested that APD ameliorates SAP by removing the PAAF. However, the mechanism underlying the success of APD treatment remains poorly understood. In the present study, we aimed to explore the possible mechanism by which APD ameliorates SAP.
The key issue in treating SAP is to control the activated inflammatory cascade and restore immune homeostasis. Peritoneal macrophages (PMs), crucial inflammatory cells in the abdominal cavity, are implicated in the initiation and progression of SAP in the early stage, and the function of PMs is regulated by the PAAF. In this study, we found that APD treatment exerts anti-inflammatory effects by regulating the M2 polarization of PMs, providing novel insights into the mechanisms underlying the therapeutic effect of APD.
The aim of this study was to determine the polarization phenotypes of PMs and the corresponding inflammatory responses in a rat model of SAP following APD treatment and to explore the possible mechanism by which APD treatment ameliorates SAP.
The effect of APD on the polarization response of PMs was determined in an SAP rat model induced by 5% Na-taurocholate retrograde injection and in a peritoneal inflammatory environment simulated by adding peritoneal lavage to culture medium in vitro. HE staining and measurement of the levels of amylase, lipase, and inflammatory mediators were performed. The M1/M2 phenotype ratio of PMs was identified by flow cytometry and RT-PCR. The distribution of macrophages and their protein expression in the pancreas were determined by immunofluorescence staining and Western blot.
APD treatment ameliorates SAP by significantly reducing the pathological scores and the levels of amylase, lipase, tumor necrosis factor-α, and interleukin (IL)-1β. Importantly, APD treatment polarizes PMs towards the M2 phenotype and increases the anti-inflammatory mediators IL-4 and IL-10 in the peritoneal lavage. Furthermore, PMs exhibited a trend towards the M2 phenotype in a simulated peritoneal inflammatory environment in vitro. Finally, APD treatment increased the number of M2 macrophages and upregulated the expression of the anti-inflammatory protein Arg-1 in the pancreas of SAP rats.
APD treatment exerts anti-inflammatory effects by regulating the M2 polarization of PMs, providing novel insights into the mechanisms underlying its therapeutic effect.
Our study provided evidence for the first time that APD ameliorates inflammation in rats with SAP by regulating PM M2 polarization. However, solid evidence that APD polarizes PMs to the M2 phenotype and the underlying molecular mechanism still need to be explored. Furthermore, future research should focus on the effect of M2 macrophages on immune homeostasis restoration and tissue repair in the injured pancreas.