Mar 20, 2002

Protease inhibition in the intestinal lumen: attenuation of systemic inflammation and early indicators of multiple organ failure in shock

H MitsuokaGeert W Schmid-Schönbein


Our recent evidence suggests that pancreatic digestive enzymes in the lumen of the intestine may play a major role in the production of cardiovascular stimulatory factors during splachnic artery occlusion and reperfusion. These stimulators are detected in plasma, but their origin and mechanism of production has remained uncertain. We examine here in the rat the role of pancreatic enzymes with and without administration of a serine protease inhibitor (FOY) into the lumen of the small intestine during splanchnic artery occlusion (90 min) and reperfusion (120 min). In the presence of pancreatic enzyme inhibition in the lumen of the intestine, there is significantly enhanced survival rate, lower levels of inflammatory mediator production, the femoral artery blood pressure is maintained close to control levels, and there are significantly lower levels of cell activators in plasma. These results support the hypothesis that pancreatic enzymes may escape across the brush border barrier during intestinal ischemia and thereby initiate the production of a powerful set of cytotoxic mediators. Blockade of pancreatic enzymes in the lumen of the intestine may be a tool to interfere with inflammation and early indicators of multiorgan failure.

Mentioned in this Paper

Splanchnic Circulation
Entire Lumen of Body System
Serine Proteinase Inhibitors, Exogenous
Serine Proteinase Inhibitors
Diastolic Blood Pressure
Small Intestinal Wall Tissue
Entire Femoral Artery

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Bone Marrow Neoplasms

Bone Marrow Neoplasms are cancers that occur in the bone marrow. Discover the latest research on Bone Marrow Neoplasms here.

IGA Glomerulonephritis

IgA glomerulonephritis is a chronic form of glomerulonephritis characterized by deposits of predominantly Iimmunoglobin A in the mesangial area. Discover the latest research on IgA glomerulonephritis here.

Cryogenic Electron Microscopy

Cryogenic electron microscopy (Cryo-EM) allows the determination of biological macromolecules and their assemblies at a near-atomic resolution. Here is the latest research.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

LRRK2 & Immunity During Infection

Mutations in the LRRK2 gene are a risk-factor for developing Parkinson’s disease. However, LRRK2 has been shown to function as a central regulator of vesicular trafficking, infection, immunity, and inflammation. Here is the latest research on the role of this kinase on immunity during infection.

Antiphospholipid Syndrome

Antiphospholipid syndrome or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable state caused by the presence of antibodies directed against phospholipids.

Meningococcal Myelitis

Meningococcal myelitis is characterized by inflammation and myelin damage to the meninges and spinal cord. Discover the latest research on meningococcal myelitis here.

Alzheimer's Disease: MS4A

Variants within membrane-spanning 4-domains subfamily A (MS4A) gene cluster have recently been implicated in Alzheimer's disease by recent genome-wide association studies. Here is the latest research.