Action sites of antiallergic drugs on human neutrophils.

Abstract

Abstract-Sites of the inhibitory action of antiallergic drugs (azelastine, oxatomide, tranilast, repirinast and amlexanox) on human neutrophils were investigated by measuring leukotriene B4 formation, arachidonic acid release and superoxide generation. Results obtained in this study were as follows: (1) Formations of leukotriene B4 by neutrophils activated with a calcium ionophore (A23187) were effectively inhibited by all types of antiallergic drugs examined here, although the required concentrations were within a range of 20-200 /tM. (ii) Releases of arachidonic acid from activated cells were diminished by azelastine and oxatomide that were classified as basic antiallergic drugs. On the contrary, acidic antiallergic agents including repirinast, amlexanox and tranilast enhanced the arachidonic acid liberation. (iii) Generations of superoxide from neutrophils activated with either phorbol 12-myristate 13-acetate or n-formyl-methionyl-leucyl-phenylalanine were effectively diminished only by the basic antiallergic drugs.

Effects of Azelastine on Neutrophil Chemotaxis, Phagocytosis and Oxygen Radical Generation.

“…Taniguchi et al (13,14) have previously reported that azelastine inhib its the amount of 02 generated by neutro phils, and this was confirmed by the results of the present investigation. In addition, our re sults show that the drug reduced the amount of H202 and OH generation by neutrophils, respectively.…”

“…Furthermore, 02 gen eration by phorbol 12-myristate 13-acetate (PMA)-stimulated neutrophils is also reduced in the presence of the drug (14). These reports seem to indicate that azelastine may inhibit the process of phospholipase A2 activation and/or the mobilization of calcium from the intracellular storage sites.…”

“…Regarding its mechanisms of action, the drug has been demonstrated to inhibit not only histamine release but also leukotriene re lease, and it also antagonizes histamine as well as leukotrienes (10)(11)(12). It has been recently reported that azelastine decrease 02 genera tion by neutrophils (13,14). However, the effects on neutrophil chemotaxis, phagocytosis and each kind of ROS, especially OH which is the most toxic oxidant, generated by both neutrophils and the xanthine-xanthine oxidase system, have not yet been examined.…”

A Japanese Patient with Familial Mediterranean Fever Associated with Compound Heterozygosity for Pyrin Variant E148Q/M694I

“…Unfortunately the above drugs were either only partially effective in our patient or could not be used at all. Accordingly we focused on colchicine's characteristic function of inhibiting neutrophil chemotactic activity (12) and found that the anti-allergic drug azelastine also inhibits neutrophil chemotaxis (13). Azelastine, like colchicine, successfully reduced the frequency and degree of the attacks in the present patient.…”

“…Accordingly we needed to seek another treatment and focused on colchicine's characteristic function: inhibition of neutrophil chemotactic activity (12). We searched for another drug having a similar function and found that azelastine, which is an anti-allergic drug, also inhibits neutrophil chemotaxis (13). We have since been administering 4-6 mg of azelastine to her daily and her attacks of fever and polyserositis have decreased.…”