THE PRIMING EFFECT OF GEMFIBROZIL ON REACTIVE OXYGEN-METABOLISM OF PHAGOCYTIC LEUKOCYTES - AN INTRIGUING SIDE-EFFECT

Gemfibrozil is an antihyperlipidaemia agent used in therapy to reduce the occurrence of coronary heart disease. Considering the biochemical and pharmacological peculiarities of this class of drugs, we investiga ted the influence of a single oral therapeutic dose of gemfibrozil on the reactive oxygen metabolism of phagocytic leucocytes. Analysis was carried out adopting a chemiluminescence assay. Results clearly indica te that gemfibrozil, acting as a primer, significantly enhances the in duced reactive-oxygen-species (ROS) production by overall blood phagoc ytes (increment of Stimulation Index (SI) = + 52% with respect to time 0 values; P < 0.01), by polymorphonuclear leucocytes (increment of SI = + 28% with respect to control values; P < 0.01) and by monocytes (i ncrement of SI = + 83% with respect control values; P < 0.001), when t hese cells are stimulated by phorbol myristate acetate. This iatrogeni c derangement of ROS metabolism could explain, at least in part, the o ccurrence of some side effects that occur in treatment with fibrates. (C) 1997 Elsevier Science B.V.