Journal of physiology and pharmacology : an official journal of the Polish Physiological Society
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Although paracetamol potently reduces pain and fever, its mechanism of action has so far not been satisfactorily explained. It inhibits both COX-1 and COX-2 weakly in vitro, but reduces prostaglandin synthesis markedly in vivo. In mouse macrophage J774.2 cells, COX-2 induced for 48 hr with high concentrations of NSAIDs is more sensitive to inhibition with paracetamol than endotoxin-induced COX-2. ⋯ Inhibition of the activity of this late-appearing COX-2 with indomethacin or a selective COX-2 inhibitor, delays resolution and the inflammation is prolonged. Cultured lung fibroblasts also express COX-2 activity after stimulation with IL-1beta which is highly sensitive to inhibition with paracetamol. Thus, evidence is accumulating for the existence of a COX-2 variant or a new COX enzyme which can be inhibited with paracetamol.