Novel therapeutic targets for acute pancreatitis and associated multiple organ dysfunction syndrome.
Acute pancreatitis is a common clinical condition. The exact mechanisms by which diverse etiological factors induce an attack are unclear but once the disease process is initiated, common inflammatory and repair pathways are invoked. Acinar cell injury early in acute pancreatitis leads to a local inflammatory reaction; if marked, this leads to a systemic inflammatory response syndrome (SIRS). An excessive SIRS leads to distant organ damage and multiple organ dysfunction syndrome (MODS). MODS associated with acute pancreatitis is the primary cause of morbidity and mortality in this condition. The systemic effects of acute pancreatitis have many similarities to those of other conditions such as septicemia, severe burns and trauma. Potentially, there is a therapeutic window between symptom onset and the development of distant organ damage in acute pancreatitis, when anti-inflammatory therapy may be of use. Recent studies conducted by us and other investigators have established the critical role played by inflammatory mediators such as TNF-alpha, IL-1beta, IL-6, IL-8, CINC/GRO-alpha, MCP-1, PAF, IL-10, CD40L, C5a, ICAM-1, and Substance P in acute pancreatitis and the resultant MODS. It is reasonable to speculate that elucidation of the key mediators in acute pancreatitis coupled with the discovery of specific inhibitors will make it possible to develop a clinically effective anti-inflammatory therapy.
Bhatia
M
M
Department of Pharmacology, National University of Singapore, Singapore. mbhatia@nus.edu.sg
D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology / Q000627:therapeutic use; D015850:Interleukin-6 / Q000494:pharmacology / Q000627:therapeutic use; D009102:Multiple Organ Failure / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D010195:Pancreatitis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D015850:Interleukin-6; D016753:Interleukin-10