Studies on the mechanism of kinin formation in inflammation

Injection of autologous plasma into the subcutaneous space leads to kinin formation in man. Kinin formation was also observed after similar injections of homologous plasma in the rat, dog and guinea-pig. The material withdrawn from the subcutaneous tissue following the injection of plasma was characterized as kinin by inhibition of its formation with trasylol, by inactivation with chymotrypsin and by its pharmacologic effects.2. Kinins were also demonstrated in subcutaneous tissue following injections of compound 48/80, a histamine liberator.3. A slightly acid pH greatly favours the accumulation of kinins in subcutis.4. Human plasma kallikrein was not activated in vitro by histamine, serotonin, nicotonic acid or endotoxin. Human polymorphonuclear leukocytes initiated the formation of kinins in plasma.5. It is suggested that in inflammation, ;primary mediators' such as histamine, do not activate plasma kallikrein directly, but rather increase vascular permeability, permitting plasma to enter the extravascular space where conditions for activation exist. Kinin accumulation is enhanced in inflammation where pH is slightly lowered.