Microsomal prostaglandin E synthase-1 (mPGES-1) constitutes a drug target for inflammation, fever and pain. mPGES-1 catalyzes the biosynthesis of prostaglandin (PG) E₂ from cyclooxygenase (Cox) -derived PGH₂, which in turn is derived from arachidonic acid. mPGES-1 is mainly associated with inflammation and it is known to be up regulated by various pro-inflammatory cytokines like IL-1 beta and TNF-alpha. Mice devoid of mPGES-1 activity display resistance to development of experimental arthritis, fever, pain, symptoms following stroke, atherosclerosis and breathing anomalies induced by hypoxia. Conversely, the enzyme seems to have a protective role in wound healing and remodeling following myocardial infarction. Inhibitors of mPGES-1 have been developed by several groups. However, their characterization in animal models of inflammation, or other models previously used to study mPGES-1 knock-out mice, remains limited. One reason is the fact that a majority of the potent inhibitors of human mPGES-1 are significantly less potent or even completely inactive towards rodent mPGES-1. In addition, the impact of mPGES-1 inhibitors on the prostaglandin profile should be further investigated in various cells and in vivo systems, as their effects but also side-effects will largely depend on the particular prostaglandin profile they elicit. In this presentation, an update will be provided on the characterization of mPGES-1 inhibitors by us and others.

Disclosure of Interest P.-J. Jakobsson Consultant for: NovaSAID AB

DOI 10.1136/annrheumdis-2014-eular.6215