Fire in the belly: A scoping review of the immunopathological mechanisms of acute pancreatitis

Abstract

IntroductionAcute pancreatitis (AP) is characterised by an inflammatory response that in its most severe form can cause a systemic dysregulated immune response and progression to acute multi-organ dysfunction. The pathobiology of the disease is unclear and as a result no targeted, disease-modifying therapies exist. We performed a scoping review of data pertaining to the human immunology of AP to summarise the current field and to identify future research opportunities.MethodsA scoping review of all clinical studies of AP immunology was performed across multiple databases. Studies were included if they were human studies of AP with an immunological outcome or intervention.Results205 studies met the inclusion criteria for the review. Severe AP is characterised by significant immune dysregulation compared to the milder form of the disease. Broadly, this immune dysfunction was categorised into: innate immune responses (including profound release of damage-associated molecular patterns and heightened activity of pattern recognition receptors), cytokine profile dysregulation (particularly IL-1, 6, 10 and TNF-α), lymphocyte abnormalities, paradoxical immunosuppression (including HLA-DR suppression and increased co-inhibitory molecule expression), and failure of the intestinal barrier function. Studies including interventions were also included. Several limitations in the existing literature have been identified; consolidation and consistency across studies is required if progress is to be made in our understanding of this disease.ConclusionsAP, particularly the more severe spectrum of the disease, is characterised by a multifaceted immune response that drives tissue injury and contributes to the associated morbidity and mortality. Significant work is required to develop our understanding of the immunopathology of this disease if disease-modifying therapies are to be established.

B Cells and Double-Negative B Cells (CD27−IgD−) Are Related to Acute Pancreatitis Severity

“…Similar to what happens in SIRS, peripheral blood lymphocyte depletion in acute pancreatitis may result from both excessive apoptosis and migration to the site of inflammation as has been previously hypothesized [29,30]. Regarding more detailed lymphocyte profiling, most studies have explored T lymphocytes, showing that acute pancreatitis results in the systemic activation of T cells [31,32]. Among T cells, it has been shown that there is a significant depletion of the CD4 + population, while CD8 + cell levels were reported to be present in the normal ranges [29].…”

The relationship between inflammatory cytokines and in‐hospital complications of acute pancreatitis

“…Inflammatory mediators further secrete by infiltrating immune-related cells, increase vascular permeability, cause neutrophil extravasation and activation, edema and microvascular disorder, and ultimately lead to hypoxia and tissue damage. 20 The results of this study showed that the levels of seven out of 12 cytokines were significantly higher in the SAP group than in the mild or moderate AP group, namely IL-1β, IL-5, IL-6, IL-8, IL-10, IL-17, TNF-α. Some studies have pointed out that among the many cytokines, TNF-α is the earliest and most widely biologically effective cytokine, and also a key factor in causing SIRS and complications.…”

“…Damaged acinar cells release damage‐associated molecular patterns, which are recognized by pattern recognition receptors (PRRs), and PRRs activate tissue and peripheral blood leukocytes and trigger the release of inflammatory cytokines. Inflammatory mediators further secrete by infiltrating immune‐related cells, increase vascular permeability, cause neutrophil extravasation and activation, edema and microvascular disorder, and ultimately lead to hypoxia and tissue damage 20 …”

“…Inflammatory mediators further secrete by infiltrating immune‐related cells, increase vascular permeability, cause neutrophil extravasation and activation, edema and microvascular disorder, and ultimately lead to hypoxia and tissue damage. 20 …”

Pro-inflammatory cytokines stimulate CFTR-dependent anion secretion in pancreatic ductal epithelium

“…Acute pancreatitis is an inflammatory disease of the exocrine pancreas, which may develop under sterile conditions and is thought to be instigated by acinar cell injury [ 1 , 2 ]. Apart from transient obstruction of the pancreatic ducts by gallstones, which causes bile to enter the pancreatic ductal tree, the most common causes of acute pancreatitis are alcohol abuse and hypertriglyceridemia [ 2 , 3 ]. The inflammatory response may resolve without specific treatment within a few days, or progress to systemic inflammation, culminating in a life-threatening failure of organs outside the pancreas [ 2 ].…”