An extracorporeal filtration and detoxification system and method generally comprise separating ultrafiltrate from cellular components of blood, treating the ultrafiltrate independently of the cellular components in a recirculation circuit, recombining treated ultrafiltrate and the cellular components, and returning whole blood to the patient. A recirculation circuit generally comprises an active cartridge including active cells operative to effectuate a selected treatment in some embodiments, the active cells are the C3A cell line.