title: Prostanoids as friends, not foes: further evidence from the interference by cycloxygenase-inhibitory drugs when inducing tolerance to experimental arthritigens in rats.
abstract: Pharmacologists have generally been prejudiced against prostanoids, uncritically accepting their suppression as desirable therapy, especially for 'quick-fix' analgesia. This myopic perception for a long time ignored (a) the essentiality of prostanoid precursors in nutrition, (b) the physiological protective functions of natural prostaglandins (PGs) (vasculature, stomach, kidney), (c) resolution of inflammation after the expression of COX-2 and (d) increasing therapeutic use of either synthetic PGs (for erectile dysfunction, ophthalmic disorders, inducing parturition, etc) or their natural precursors, e.g., omega3-rich polyunsaturated oils, to treat arthritis. Experimental studies in rats have indicated that prostaglandins (E series) are (i) useful, perhaps auto-regulators of established immunoreactivity and (ii) able to amplify (or even induce) anti-inflammatory activity with other agents. Furthermore, anti-prostanoid therapy (APT) can be arthritigenic!!, interfering with the acquisition of tolerance to some arthritigens. For patients with rheumatoid arthritis this additional side-effect of APT, barely recognised to date, may actually perpetuate their arthritis by impairing prostanoid-mediated remission processes. Hopefully, recent adverse publicity about COX-2 inhibitory drugs might stimulate serious re-assessment of some traditional anti-inflammatory therapies with low APT activity for the management of both acute pain (non-addictive cannabinoids, celery seed, etc.) and chronic inflammation, e.g., Lyprinol (a mussel lipid extract).
authors.affiliation: Therapeutics Research Unit, Department of Medicine, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Qld. 4102, Australia. whitehousemd@spin.net.au
authors.forename: Michael W
authors.initials: MW
authors.lastname: Whitehouse
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D004361:Drug Tolerance; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D007279:Injections, Subcutaneous; D008055:Lipids / Q000633:toxicity; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D011453:Prostaglandins / Q000502:physiology* / Q000627:therapeutic use; D011720:Pyrazoles / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013185:Squalene / Q000633:toxicity; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D016861:Cyclooxygenase Inhibitors; D008055:Lipids; D011453:Prostaglandins; D011720:Pyrazoles; D013449:Sulfonamides; C418997:lyprinol; D013185:Squalene; D011239:Prednisolone; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D001241:Aspirin