TNF and edema: Oedema formation induced by carrageenan is described as a biphasic event: the first phase (0–2 hours) is mediated by histamine and serotonin followed by bradykinin, prostaglandins, and lysosome, while the late phase (2–6 hours) is related to the production of TNF, interleukins (IL-1β and IL-6), and nitric oxide [32].