0533. For some of those who thought they knew everything about lipid mediators…

A previous abstract (48/2004) covered the molecular biological issues involved in the recognition of COX-2 inhibitors as potential dangers when used for chronic management of inflammatory conditions. To summarise, the targeted inhibition reduced certain favourable endothelial actions while leaving the unfavourable to act unopposed. Now, as the dust settles on the first verdict against this class of drug ($253 punitive damages) we are also seeing more of the complexity of the type of pathways involved and begin to understand potential consequences of interfering with these pathways. Terms such as lipidomics, lipoxins and resolvins have entered the literature, and intake and levels of the essential omega-6 and -3 fatty acids have been shown to influence the concentrations of these newly-described mediators. Apparently our ancestors had ratios of 1:1 for these essential fatty acids whereas today we are closer to 15:1 (omega-6:omega-3). Therapeutic interventions have focused on inhibition of many of the omega-6 (arachidonic acid) products, but given that we now know the importance of omega-3 and also the importance of the lipoxin:resolvin balance, we should probably be doing more in terms of diet to restore the omega-6:omega-3 balance, as well as focusing on modulating rather than simply inhibiting mediator formation.

Read more:
New Engl J Med 2004;351:1707-9 and 1709-11
Lancet 2005;366:618-20
Biomed Pharmacother 2002;56:365-79
Am J Physiol Renal Physiol 2004;286:F189-201