5-Lipoxygenase activation in psoriasis: a dead issue?
It has been suggested in the literature that 5-lipoxygenase activation may be an important pathological event in psoriasis and that 5-lipoxygenase inhibitors may thus have some beneficial therapeutic effect in this disease. This is because (1) neutrophil activation is a prominent feature of the disease, (2) leukotriene B4 is a potent chemotactic agent for neutrophils and is present in psoriatic lesions, (3) 5-lipoxygenase is present in human epidermis, (4) inhibition of 5-lipoxygenase may affect the disease. These concepts are questioned, and in particular it is suggested that (1) the leukotriene B4-like material found in psoriatic skin has never been shown to have the correct stereochemistry to indicate that it is 5-lipoxygenase derived, (2) there is no convincing evidence for the presence of the 5-lipoxygenase enzyme in human skin, (3) drugs purported to have some benefit in psoriasis through 5-lipoxygenase inhibitory mechanisms act through other mechanisms and (4) selective leukotriene biosynthesis inhibitors have no therapeutic utility in psoriasis. It is concluded that 5-lipoxygenase activation does not play a significant role in the pathology of psoriasis and therefore selective leukotriene biosynthesis inhibitors would have no significant role in the treatment of this disease.
Ford-Hutchinson
A W
AW
Department of Pharmacology, Merck Frosst Centre for Therapeutic Research, Dorval, Que., Canada.
D001094:Arachidonate 5-Lipoxygenase / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects; D004817:Epidermis / Q000201:enzymology; D006801:Humans; D020024:Leukotriene Antagonists; D007975:Leukotriene B4 / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects; D011565:Psoriasis / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology
D020024:Leukotriene Antagonists; D007975:Leukotriene B4; D001094:Arachidonate 5-Lipoxygenase