Kallikrein-kinin in infection and cancer

This review article describes the mechanism of enhancement of vascular perm eability in infectious disease and cancer. This phenomenon is primarily med iated by bradykinin, nitric oxide and other unique vascular mediators. They are highly intermingled with each other in these disease stares. Furthermo re, these mediators are elicited in various in vivo settings most frequentl y induced by bacterial proteases, and indirect or direct activation of kall ikrein-kinin cascade at one or more steps. The key steps involve bacterial proteases or cellular components including lipopolysaccharides. Thus, the u se of appropriate protease inhibitors or antagonists, or scavengers in the case of nitric oxide, superoxide or peroxynitrite, are anticipated to atten uate the clinical manifestation induced by such mediators. It also explaine d that fluid accumulation in ascitic or pleural compartments in the case of carcinomatosis in terminal cancer patients can be largely attributed to br adykinin or related mechanism. Systemic bacterial dissemination is also fac ilitated by bradykinin, or suppressed by kinin antagonists as well as by th e inhibition of kinin production, respectively. Thus, control of the level of such vascular mediators appears important both in infectious disease and in cancer, alpha(1)-Protrase inhibitor, which inhibits neutrophil elastase , is inactivated by oxidative metabolites such as superoxide and peroxynitr ite, and this effect activates matrix metalloproteinases. This indicates th at oxidative stress activates proteolytic potential, and thus accelerates t he degenerative process upon infection. (C) 1999 Elsevier Science B.V. All rights reserved.