Inflammation Cascade

Function of C1 Esterase Inhibitor in the Normal Contact Pathway

The body relies on chemical pathways to mediate normal inflammatory, immune and coagulation responses. These pathways are known as the Complement, Contact, and Coagulation systems. Across all of these pathways, a protein called C1 esterase inhibitor or C1-INH - a normal human protein that regulates these responses high up in each pathway - plays an important role in mediating inflammation, injury, and tissue damage.

The Contact System is the pathway that controls swelling following injury. C1-INH and several other proteins are components of the contact system which circulate in plasma. When tissues are injured, these proteins interact to initiate an inflammatory response that provides surrounding tissues with fluid to assist in healing. C1-INH regulates the inflammatory response by limiting the amount of fluid that is released.

After an injury, several proteins interact to cause inflammation, which is primarily mediated by one key protein called bradykinin. The build-up of bradykinin dilates local capillaries and increases vascular permeability by opening channels in the capillary walls, allowing fluid to enter the tissues. The influx of dissolved proteins provides protection and pain mediation at the injury site.

In order to stop the inflammation feedback loop, C1-INH binds irreversibly to proteins - namely factor XIIa and kallikrein - which, in turn, breaks the swelling feedback loop and slows bradykinin release. In the absence of bradykinin, fluid release stops; capillary walls become less permeable; and the swelling can go down as fluids are re-absorbed back into the body. Without C1-INH, this inflammatory cascade could not be controlled.