LEUMEDIN NPC-15669 INHIBITS ANTIGEN-INDUCED RECRUITMENT OF INFLAMMATORY CELLS INTO THE CANINE AIRWAYS

We studied the effects of NPC 15669, a member of a new class of anti-i nflammatory drugs called leumedins, on chemotaxis of both human eosino phils and neutrophils and on Mac-1 receptor upregulation on stimulated eosinophils in vitro. Then, we examined the effect of NPC 15669 on an tigen-induced eosinophil and neutrophil recruitment and subsequent air way hypersecretion (indicated by an increase in lysozyme concentration ) in the allergic dog trachea in vivo. NPC 15669 inhibited eosinophil chemotaxis in vitro at a drug concentration of 10(-5) M (mean inhibiti on, 48.2%) without affecting Mac-1 receptor upregulation on stimulated eosinophils. NPC 15669 also inhibited neutrophil chemotaxis: at 10(-5 ) M, NPC 15669 inhibited neutrophil chemotaxis by a mean of 29.7%. In allergic dogs in vivo, NPC 15669 (10(-5) M) prevented antigen-induced recruitment of eosinophils and neutrophils and prevented the increase in elastase and lysozyme concentrations. We conclude that NPC 15669 is an effective inhibitor of antigen-induced leukocyte recruitment and e lastase release and subsequent hypersecretion in airways.