Published online Oct 28, 2017. doi: 10.3748/wjg.v23.i40.7242
Peer-review started: August 19, 2017
First decision: September 6, 2017
Revised: September 22, 2017
Accepted: September 29, 2017
Article in press: September 26, 2017
Published online: October 28, 2017
Pancreatic fibrosis is a common pathological feature characteristic of chronic pancreatitis (CP). As the necrosis-fibrosis sequence plays an important role in the underlying pathogenesis of CP, pancreatic fibrosis commonly develops after repeated inflammation. Macrophages are important inflammatory cells that can also promote fibrogenesis by interfering with the synthesis and degradation of the extracellular matrix. This has been confirmed in models of liver fibrosis and renal fibrosis, but any role of macrophages in pancreatic fibrosis has remained unclear. A traditional Chinese medicinal formula, Dachaihu decoction (DCHD), has been widely used in the clinical treatment of AP, and recently, DCHD was used to treat CP, which significantly improved the patient’s clinical symptoms, but, again, the underlying mechanism has been unclear.
CP is a progressive inflammatory disease characterized by irreversible injury to the pancreas leading to endocrine and exocrine dysfunctions that pose serious threats to human health, because the pathogenesis is unclear, and few treatments are available. Recent studies suggested that DCHD can significantly improve the clinical symptoms of CP patients, such as abdominal pain, abdominal distension, loss of appetite and others. However, DCHD cannot be widely used clinically because the therapeutic mechanism of action remains unclear.
The aim was to explore the role played by macrophages in the pathogenesis of CP to further elucidate the mechanisms of CP. In addition, they assessed the efficacy of DCHD in treating CP in animal experiments to determine the mechanism involved, providing an experimental basis for promoting the use of DCHD in clinical practice.
KunMing mice were randomly divided into a control group, CP group, and DCHD group. In the CP and DCHD groups, mice were intraperitoneally injected with 20% L-arginine (3 g/kg twice a day, 1 d a week). Mice in the DCHD group were given DCHD (14 g/kg per day) intragastrically for 1 wk after CP induction. The animals were anesthetized and sacrificed at 2 wk, 4 wk and 6 wk after study commencement. Pancreatic morphology and the extent of fibrosis were assessed using hematoxylin and eosin and Masson staining. Serum interleukin-6 (IL-6) levels were assessed by enzyme-linked immunosorbent assay. Double immunofluorescence staining was performed to assess the co-expression of F4/80 and IL-6 in the pancreas. The mRNA levels of inflammatory factors including monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α) and IL-6 were determined by real time-polymerase chain reaction. Western blotting was used to measure fibronectin (FN) levels in the pancreas.
We found that macrophage infiltration was significantly increased in the CP group, and the IL-6 levels in serum and IL-6 mRNA levels in the pancreas were also increased in the CP group. Further, immunofluorescent double-staining of F4/80 and IL-6 revealed that macrophages were the main source of the IL-6. In addition, DCHD ameliorated pancreatic fibrosis, inhibited the pancreatic infiltration of macrophages in the CP group, and reduced the release of cytokines IL-6, MCP-1 and MIP-1α mRNA, and FN levels. However, our work had certain limitations. We confirmed that the effect of macrophages on CP is related to IL-6, but the detailed mechanism of IL-6 on CP progression was not further explored. In addition, DCHD is effective in CP treatment, but its in-depth mechanism was not studied further.
The authors confirmed that macrophages are involved in the development of pancreatic fibrosis and may constitute a new therapeutic target. In addition, DCHD can ameliorate pancreatic fibrosis by inhibiting macrophage infiltration and inflammatory factor secretion in the pancreas.