Local and Systemic Expression of Immunomodulatory Factors in Chronic Pancreatitis

Abstract

Inflammatory and fibrotic events that drive chronic pancreatitis (CP) are likely orchestrated via signaling of soluble cytokines and chemokines systemically and within the pancreas. However, a comprehensive summary of the expression of such factors during CP has not been reported to date. This information is important given continued interest in targeting cytokines that influence CP pathogenesis. Reported data on the expression change of soluble immunomodulatory factors in human CP patients were identified via a literature search using a single search term. Thirty-one articles meeting the pre-specified inclusion criteria were identified to generate a compiled data summary. Compiled data demonstrated up-regulation of several factors in the blood or pancreas microenvironment of CP patients. Nine factors were elevated in both compartments, including fractalkine, interferon gamma (IFN-γ), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), macrophage inhibitory cytokine 1 (MIC-1), neutrophil gelatinase-associated lipocalin (NGAL/LCN2), transforming growth factor beta (TGF-β), and tumor necrosis factor alpha (TNF-α). Most up-regulated factors could be classified into one of several functional groups, including inflammation, chemotaxis, angiogenesis, bone remodeling, extracellular matrix remodeling, and pain. Following further validation, these factors may be used as biomarkers for disease diagnosis, identification of comorbidities, or as potential therapeutic targets.

Systemic inflammation contributes to impairment of quality of life in chronic pancreatitis

“…Several pro-inflammatory mediators are associated with reduced quality of life in general or with worse specific function and symptom scores of the QLQ-C30 and PAN 28 questionnaires. While some of the inflammatory mediators were described in recent clinical and pre-clinical studies dealing with this issue, changed serum levels of most of the identified inflammatory mediators have not been associated to CP yet 12,18 . Patients with CP suffer from a diminished quality of life in general.…”

Nardilysin inhibits pancreatitis and suppresses pancreatic ductal adenocarcinoma initiation in mice

“…It is known that inflammation and fibrosis in chronic pancreatitis are likely orchestrated via signalling of soluble cytokines and chemokines 39. We found that the expression of chemokines including Mcp1 , Ccl5 , Cx3cl1 and Icam1 was significantly increased in isolated Nrdc-cKO acinar cells at 3 weeks of age, when immune cell infiltration was not yet observed and that the expression of Cxcl10 was markedly increased in Nrdc- deleted acinar cells in ex vivo culture experiments.…”

Oncostatin M promotes the osteogenic differentiation of mouse MC3T3‑E1osteoblasts through the regulation of monocyte chemotactic protein‑1

“…The activation and resorption of the bone matrix, and the formation of new bones are processes that occur during the bone remodeling process ( 31 ). Chemokines are small proteins weighing 8–10 kDa, which serve important roles in host defense systems and help to maintain normal tissues status ( 32 , 33 ).…”