Selective plasma kallikrein inhibitor attenuates acute intestinal inflammation in Lewis rat.

Abstract	A specific plasma kallikrein inhibitor, Bz-Pro-Phe-boroArg (P8720), was used to define the relationship between the kallikrein-kinin (K-K) system and acute intestinal inflammation induced by bacterial peptidoglycan-polysaccharide (PG-APS) in Lewis rats. Group I received human serum albumin (HSA) intramurally in the intestine and was treated with HSA. Group II received PG-APS and was treated with P8720. Group III received PG-APS and was treated with HSA. P8720 attenuated the decrease of high-molecular-weight kininogen and factor XI activity (group II vs group III, P < 0.01). P8720 therapy significantly but modestly decreased acute intestinal inflammation measured by gross gut score (P < 0.01) and more dramatically reduced the tissue myeloperoxidase activity (P < 0.05), a measure of granulocyte recruitment, in group II compared with group III. We conclude that the K-K system is directly involved in the pathogenesis of the acute phase of experimental acute inflammation. A specific inhibitor may modulate inflammatory bowel disease.
Authors	A Stadnicki, R A DeLa Cadena, R B Sartor, D Bender, C A Kettner, H C Rath, A Adam, R W Colman
Journal	Digestive diseases and sciences (Dig Dis Sci) Vol. 41 Issue 5 Pg. 912-20 (May 1996) ISSN: 0163-2116 [Print] United States
PMID	8625762 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Boron Compounds Enzyme Inhibitors Oligopeptides Peptidoglycan Serum Albumin benzoyl-prolyl-phenylalanyl-boroarginine Kallikreins
Topics	Acute Disease Animals Boron Compounds (therapeutic use) Disease Models, Animal Drug Evaluation, Preclinical Enzyme Inhibitors (therapeutic use) Female Humans Inflammatory Bowel Diseases (blood, chemically induced, drug therapy) Kallikrein-Kinin System (drug effects) Kallikreins (antagonists & inhibitors, metabolism) Oligopeptides (therapeutic use) Peptidoglycan Rats Rats, Inbred Lew Serum Albumin (therapeutic use) Specific Pathogen-Free Organisms Streptococcus pyogenes

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