Ketone bodies affect the enzymatic activity of macrophage migration inhibitory factor Ja ´nos Garai a , Tama ´s Lo ´ra ´nd b , Vale ´ria Molna ´r a, T a Department of Pathophysiology, University of Pe ´cs, Medical School, Pe ´cs, H-7624 Pe ´cs, Szigeti u. 12, Hungary b Department of Medicinal Chemistry, University of Pe ´cs, Medical School, Pe ´cs, Hungary Received 21 January 2005; accepted 25 March 2005 Abstract Macrophage migration inhibitory factor (MIF), a long known proinflammatory cytokine exhibits perplexing enzymatic activities: tautomeric conversion of d-dopachrome and phenylpyruvate. Whether these catalytic activities bear functional relevance regarding MIF’s multifaceted roles is under current scrutiny. Nevertheless, intense search has already started for pharmacological agents that target MIF’s tautomerase activity. We have probed several antiinflammatory compounds against keto–enol (enolase) and enol–keto (ketonase) conversion of phenylpyruvate by MIF with spectrophotometry. We have identified acidic CH groups as markers of inhibitor potency toward MIF phenylpyruvate tautomerase. Among simple model molecules with strong acidic CH groups we found acetylacetone the best inhibitor particularly against the ketonase activity. Ketones of physiological importance – ketone bodies – also feature acidic CH groups and have been reported to exert certain anti- inflammatory effects. In this paper we report that ketone bodies inhibit preferentially the ketonase activity of MIF in vitro. Future studies should address whether such an interaction might operate in vivo and delineate its possible relevance concerning cytokine and non-cytokine roles of MIF. D 2005 Elsevier Inc. All rights reserved. Keywords: Ketone bodies; MIF; Tautomerase; Diketones 0024-3205/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.lfs.2005.03.010 T Corresponding author. Tel.: +36 72 536 246; fax: +36 72 536 247. E-mail address: valeria.molnar@aok.pte.hu (V. Molna ´r). Life Sciences 77 (2005) 1375 – 1380 www.elsevier.com/locate/lifescie