Interference of anti‐inflammatory and anti‐asthmatic drugs with neutrophil‐mediated platelet activation: singularity of azelastine

Abstract

The capacity of various drugs (acetylsalicylic acid (ASA), ketoprofen, diclofenac, piroxicam, BW 755C, BW A4C, nedocromil sodium and azelastine) to inhibit human polymorphonuclear neutrophil (PMN)‐mediated platelet activation was investigated. In this model, stimulated PMN release cathepsin G (Cat G), a serine proteinase which, in turn, induces platelet activation. Among the different tested drugs, azelastine (100 μm for 1 min) was the only one able to prevent platelet aggregation. The cyclo‐oxygenase inhibitors were all inactive, although used at effective concentrations as judged by inhibition of thromboxane B2 (TxB2) formation. Inhibition of platelet aggregation by azelastine was concentration‐dependent, the range of active concentrations being of 20–70 μm. Release from platelets of 5‐hydroxytryptamine was also inhibited at 30 μm and above, but never reached 100%. The inhibition by azelastine is due to an effect on both cells. Indeed, β‐glucuronidase release from activated PMN and platelet activation by purified Cat G were both affected. However, used at high concentrations (>100 μm) azelastine was toxic since it released significant amounts of lactate dehydrogenase (LDH) from PMN and platelets. These results show the capacity of azelastine, an anti‐allergic and anti‐asthmatic compound, to inhibit the cell‐to‐cell communication between PMN and platelets, an effect which may be relevant for its therapeutic efficacy or for a new application in diseases in which PMN and platelets are involved. 1991 British Pharmacological Society