In vivo models to study cyclooxygenase products in health and disease: Introduction to Part III.
Inflammation is a primordial response that protects against injury and infection with the ultimate aim of restoring damaged tissue to its normal physiological functioning state. In fact, our well-being and survival depends upon its efficiency and carefully balanced control and to which we are alerted in the form of pain, swelling, and redness. Prostaglandins (PG), lipids derived from arachidonic acid metabolism by the enzyme cyclooxygenase, are historically one of the most well-studied mediators of the acute inflammatory response; so much so that their inhibition by so-called non-steroidal anti-inflammatory drugs (NSAIDs) has been the mainstay for the treatment of diseases where inflammation becomes a pathological driving force. However, while NSAIDs relieve the symptoms of dyregulated inflammatory responses, they do not cure the underlying disease and have associated gastrointestinal and renal toxicity. These side effects arose from inhibiting constitutively expressed, protective cyclooxygenase (COX-1). Finding another inducible COX (COX-2) expressed only at sites of injury provided a new era in inflammation research and a new era in treating inflammation-driven diseases. The hope was that high levels of COX-2 expression at sites of pain and tissue injury drove that disease process and that its inhibition would possess all the benefits of traditional NSAIDS without the side effects that arise from the inhibition of protective COX-1. However, by discussing data derived from experimental disease models of acute inflammation, in this chapter we suggest that delineating between the roles of COX-1 and COX-2 might not be as simple as once thought. We provide examples of data where a pathological role for COX-1 is evident and where COX-2 is clearly protective.
Gilroy
Derek W
DW
Division of Medicine, Centre for Clinical Pharmacology, Rayne Institute, University College London, London, UK.
Stables
Melanie
M
Newson
Justine
J
D000818:Animals; D051545:Cyclooxygenase 1 / Q000276:immunology; D051546:Cyclooxygenase 2 / Q000276:immunology*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology*
D052246:Cyclooxygenase 2 Inhibitors; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2