C3 and angioedema: Antibiotics can cause angioedema through both immune-mediated and non-immune-mediated mechanisms. Immune-mediated angioedema can result from the activation of the complement system, leading to the generation of anaphylatoxins such as C3a and C5a, which can stimulate the release of histamine from mast cells. Non-immune-mediated angioedema can result from direct activation of mast cells by the antibiotic.