Hageman factor-dependent kinin activation in burns and its theoretical relationship to postburn immunosuppression syndrome and infection.

Burn injury and intradermal injection of bradykinin or histamine cause permeability changes visualized as dye-release lesions in the skin of guinea pigs injected intravenously with Evans blue dye. Antihistamine pretreatment ablates the histamine but not the effect of thermal injury or bradykinin. Bradykinin is generated via activation of Hageman factor in a two-step reaction. Steps 1 and 2 can be inhibited by corn trypsin inhibitor and soy bean trypsin inhibitors, respectively. Dye-release lesions were reduced from thermal injury and bradykinin injections when these substances were injected into the skin first. Angiotensin-converting enzyme deactivates bradykinin by degrading it. Angiotensin-converting enzyme inhibitor neutralizes angiotensin-converting enzyme. Dye-release lesions from both thermal injury and bradykinin injection were enhanced because of continued bradykinin build-up when these treatments were preceded by subcutaneous injections of angiotensin-converting enzyme inhibitor. Thus bradykinin is generated in thermal injury via the Hageman factor-dependent pathway. Hageman factor sits at the apex of a series of interrelated cascade systems, all of which impinge on the animal's immune status. Uncontrolled Hagemen factor activation in thermal injury may be the link among all the events collectively known as the "post thermal injury immunosuppression syndrome."