BACKGROUND Acute pancreatitis (AP) is an inflammatory disease, which presents with epigastric pain and is clinically diagnosed by amylase and lipase three times the upper limit of normal. The 2012 Atlanta classification stratifies the severity of AP as one of three risk categories namely, mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP). Challenges in stratifying AP upon diagnosis suggest that a better understanding of the underlying complex pathophysiology may be beneficial. AIM To identify the role of the chemokine receptor 8 ( CCR8 ), expressed by T-helper type-2 Lymphocytes and peritoneal macrophages, and its possible association to Interleukin (IL)-6 and AP stratification. METHODS This study was a prospective case-control study. A total of 40 patients were recruited from the Chris Hani Baragwanath Academic Hospital and the Charlotte Maxeke Johannesburg Academic Hospital. Bioassays were performed on 29 patients (14 MAP, 11 MSAP, and 4 SAP) and 6 healthy controls as part of a preliminary study. A total of 12 mL of blood samples were collected at Day (D) 1, 3, 5, and 7 post epigastric pain. Using multiplex immunoassay panels, real-time polymerase chain reaction (qRT-PCR) arrays, and multicolour flow cytometry analysis, immune response-related proteins, genes, and cells were profiled respectively. GraphPad Prism™ software and fold change (FC) analysis was used to determine differences between the groups. P <0.05 was considered significant. RESULTS The concentration of IL-6 was significantly different at D3 post epigastric pain in both the MAP group and MSAP group with P = 0.001 and P = 0.013 respectively, in a multiplex assay. When a FC of 2 was applied to identify differentially expressed genes using RT 2 Profiler, CCR8 was shown to increase steadily with disease severity from MAP (1.33), MSAP (38.28) to SAP (1172.45) median FC. Further verification studies using RT-PCR showed fold change increases of CCR8 in MSAP and SAP ranging from 1000 to 1000000 times when represented as Log 10 , compared to healthy control respectively at D3. The findings also showed differing lymphocyte and monocyte cell frequency between the groups. With monocyte population frequency as high as 70% in MSAP at D3. CONCLUSION The higher levels of CCR8 and IL-6 in the severe patients and immune cell differences compared to MAP and controls provide an avenue for exploring AP stratification to improve management.

Although its most well-written functions are digestion and absorption of nutrients, the gastrointestinal tract (GIT) is the most significant player in the human immune system. The GIT is home to more than 60% of the active immune cells in the entire body. Notwithstanding, the human gut is continuously exposed to antigens ingested with food and resident microorganisms. The density of microorganisms in the lumen of GIT increases aborad and is much higher in the colon. Despite a relatively low bacterial load in the small intestine, the environment is more precarious because it is nutritious and exposed to digestive enzymes. Its lining is made up of a single layer of epithelial cells covered by a thin and attenuated layer of mucus. Despite the continual exposure to the luminal antigens, the gut’s immune system is kept in a state of relative immunosuppression. The pathogenesis of some of the common non-communicable diseases includes a systemic inflammatory state initiated by dysbiosis in the gut, increased permeability of the intestinal epithelium, translocation of microbiomes or their products, and then a persistent pro-inflammatory state. Paneth cells are the key players in the innate immunity of the gut and are responsible for maintaining its integrity.

No abstract

No abstract