Inflammation is accompanied by activation of the
plasma kallikrein-
kinin system (KKS). KKS activation has been demonstrated in a variety of inflammatory human diseases. To further explore the participation of KKS in
arthritis and
inflammatory bowel disease, we used two experimental animal models in
arthritis and
enterocolitis. We found that activation of KKS is associated with
arthritis induced by
intraperitoneal injection of
peptidoglycan-
polysaccharide polymers (PG-PS) as well as the
enterocolitis and systemic
inflammation induced also by PG-PS when injected into the intestinal wall of genetically susceptible Lewis rats. We postulated that KKS participates in the pathogenesis of inflammatory reactions involved in cellular injury, coagulation, fibrinolysis,
kinin formation, complement activation,
cytokine secretion, and release of
proteases. We demonstrated that
therapy with a specific
plasma kallikrein inhibitor modulated the experimental
enterocolitis,
arthritis, and systemic
inflammation. The fact that deficiency of plasma
high molecular weight kininogen in the genetically susceptible Lewis rat results in decreased chronic
enterocolitis and systemic
inflammation also supports our hypothesis. We suggest that KKS plays a similar role in idiopathic human intestinal inflammatory disease and
arthritis, making kallikrein-kinin system
proteins appealing targets for
drug therapy in chronic inflammatory diseases such as
rheumatoid arthritis and
Crohn's disease.