C1 inhibitor (C1-INH) is a critical serpin-family protease inhibitor that regulates the complement system and controls the activation of several inflammatory pathways, most notably by inhibiting complement proteases and the contact system enzymes.
C1 inhibitor suppresses excessive inflammation by targeting proteases such as C1r, C1s (complement system), plasma kallikrein, and factor XIIa, thereby controlling vascular permeability and the generation of bradykinin.
Its actions extend to interactions with complement proteins, extracellular matrix molecules, immune cells, and even bacterial endotoxins, enhancing host defense and reducing tissue injury during inflammation or infection.
Deficiency or dysfunction of C1-INH leads to hereditary angioedema (HAE), a genetic condition marked by episodic, painful swelling (angioedema) of the subcutaneous and submucosal tissues—commonly affecting the face, airways, gastrointestinal tract, or extremities.
Most cases are due to low C1-INH levels, and fewer reflect dysfunctional protein despite normal levels.
The absence of regulation results in unchecked bradykinin production and widespread complement activation, causing fluid leakage and swelling.
Human C1-esterase inhibitor is used both as a preventive and acute treatment for hereditary angioedema, available in intravenous or subcutaneous formulations.
Hereditary angioedema is due to deficiency/dysfunction.
Predisposition to autoimmune conditions, such as with chronic deficiency.
Potential links to age-related macular degeneration if SERPING1 gene mutations are present
Direct inhibitor of endotoxin binds to LPS.
Reduces inflammation
Defensive against bacterial infection, enhancing phagocytosis
C1 inhibitor plays an essential, multi-pathway regulatory role in inflammation, complement control, and immune protection, with deficiency resulting in distinctive and potentially life-threatening disease.