Repetitive Cerulein-Induced Chronic Pancreatitis in Growing Pigs—A Pilot Study

Abstract

Chronic pancreatitis (CP) is an irreversible and progressive inflammatory disease. Knowledge on the development and progression of CP is limited. The goal of the study was to define the serum profile of pro-inflammatory cytokines and the cell antioxidant defense system (superoxidase dismutase—SOD, and reduced glutathione—GSH) over time in a cerulein-induced CP model and explore the impact of these changes on selected cytokines in the intestinal mucosa and pancreatic tissue, as well as on selected serum biochemical parameters. The mRNA expression of CLDN1 and CDH1 genes, and levels of Claudin-1 and E-cadherin, proteins of gut barrier, in the intestinal mucosa were determined via western blot analysis. The study showed moderate pathomorphological changes in the pigs’ pancreas 43 days after the last cerulein injection. Blood serum levels of interleukin (IL)-1-beta, IL-6, tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGTP), SOD and GSH were increased following cerulein injections. IL-1-beta, IL-6, TNF-alpha and GSH were also increased in jejunal mucosa and pancreatic tissue. In duodenum, decreased mRNA expression of CDH1 and level of E-cadherin and increased D-lactate, an indicator of leaky gut, indicating an inflammatory state, were observed. Based on the current results, we can conclude that repetitive cerulein injections in growing pigs not only led to CP over time, but also induced inflammation in the intestine. As a result of the inflammation, the intestinal barrier was impaired.

Does Chronic Pancreatitis in Growing Pigs Lead to Articular Cartilage Degradation and Alterations in Subchondral Bone?

“…This suggests its potential utility as a biomarker for osteoarthritis [47]. A previous analysis showed increased blood TNF-α concentrations in a pig model of CP [7], whereas in the current study, increased MMP-13 concentrations were observed in the synovial fluid. Together these data indicate that both local and systemic inflammation takes place simultaneously, as was observed in other animal [48] and clinical studies.…”

“…Previous analysis of all biochemical parameters in the serum of pigs with ceruleininduced chronic pancreatitis (CP) revealed pancreatic and intestinal inflammation, together with an associated increase in the TNF-α concentration in the mucous membrane of the duodenum and pancreas [7]. The trends observed in the data of femoral trabecular bone observed in CP pigs in the current study may be caused by the overall inflammatory state within the body, especially when other specific inflammatory markers like IL-1β, IL-6, and CRP are also elevated [7,25].…”

“…An elevated concentration of IL-10 in blood serum could indicate a cellular communication response to an overall low-grade inflammatory state. This response aims to mitigate inflammation, facilitate tissue repair, and prevent immunopathological consequences associated with chronic inflammation [7,28,29].…”

“…This model exhibited symptoms similar to those observed in humans during clinical observations. Moreover, an increase in pro-inflammatory cytokines in blood serum (interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNFα)), as well as inflammatory indicators (C-reactive protein (CRP), lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGTP), superoxide dismutase (SOD), and reduced glutathione (GSH)) were observed in the pigs, confirming systemic inflammation [7]. There is a clear association between chronic systemic inflammation and osteoporosis (OP), a systemic bone metabolic disorder characterized by deteriorating bone microarchitecture and increased bone vulnerability [8,9] which contributes to accelerated bone loss and an increased risk of fractures in affected individuals [10,11].…”

“…Thus, we hypothesized that experimental CP in young animals, leading to systemic inflammation [7], can result in the development of OA over time. The goal of the study was to analyze the basal structure of subchondral bone and articular cartilage, pro-inflammatory profile, and the content of matrix metalloproteinase-13 (MMP-13) in synovial fluid, MMP-13 and transforming growth factor β1 (TGF-β1) expression in articular cartilage in growing piglets with CP.…”