Complement in Pancreatic Disease—Perpetrator or Savior?

Abstract

The complement system is a major pillar of the humoral innate immune system. As a first line of defense against pathogens, it mediates early inflammatory response and links different branches of humoral and cellular immunity. Disorders affecting the exocrine pancreas, such as acute pancreatitis, potentially lead to a life-threatening systemic inflammatory response with aberrant activation of complement and coagulation cascades. Pancreatic proteases can activate key effectors of the complement system, which in turn drive local and systemic inflammation. Beyond that, the extent of pancreas–complement interaction covers complex pro- and anti-inflammatory mechanisms, which to this day remain to be fully elucidated. This review provides a comprehensive overview of the pathophysiological role of complement in diseases of the exocrine pancreas, based on existing experimental and clinical data. Participation of complement in acute and chronic pancreatitis is addressed, as well as its role in tumor immunology. Therapeutic strategies targeting complement in these diseases have long been proposed but have not yet arrived in the clinical setting.

Label-free serum proteomics and multivariate data analysis identifies biomarkers and expression trends that differentiate Intraductal papillary mucinous neoplasia from pancreatic adenocarcinoma and healthy controls

“…Other consistently increased proteins included four complement proteins (C2, C9, CFH, CFB). Complement proteins have been previously shown to be elevated in serum of pancreatic cancer and acute pancreatitis patients [30]. Complement cascade activation leads to persistent inflammation and activates cancer specific pathways [31,32].…”

Risk Stratification and Early Conservative Treatment of Acute Pancreatitis

“…This results in activation of other proteases, subsequently leading to cell damage. The release of oxygen-derived free radicals, pro-inflammatory cytokines (e.g., IL-1, IL-6, IL-8, TNFα, PAF), cell damage-associated patterns (e.g., free mitochondrial DNA, rise in calcium concentration), and complement activation play a pivotal role in the transformation of AP from a local into a multiorgan inflammatory process often characterized by a systemic inflammatory response syndrome (SIRS) [11, 12]. In response to pro-inflammatory cytokines, acute-phase reaction proteins are released and can be used to assess the severity of inflammation (e.g., C-reactive protein [CRP], IL-6, or procalcitonin [PCT]).…”

First Time Experience of Application of Immune Histochemical Tests of the Retroperitoneal Tissue in the Early Phase of Acute Necrotizing Pancreatitis

“…Трипсин способен расщеплять и активировать центральные компоненты комплемента, что ведет к образованию анафилотоксинов C3a и C5a, которые в свою очередь могут вызывать все классические признаки воспаления. Генерируемые продукты активации комплемента являются мощными факторами локального и системного воспаления и вносят значительный вклад в развитие ССВО [15].…”