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-inflammatory drugs called leumedins, on chemotaxis of both human eosinophils and neutrophils and on Mac-1 receptor upregulation on stimulated eosinophils in vitro. Then, we examined the effect of NPC 15669 on antigen-induced eosinophil and neutrophil recruitment and subsequent airway 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 inhibition, 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 elastase release and subsequent hypersecretion in airways.
Kaneko
T
T
Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
Jorens
P G
PG
Richman-Eisenstat
J B
JB
Dazin
P F
PF
Nadel
J A
JA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000941:Antigens / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004285:Dogs; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D009113:Muramidase / Q000378:metabolism; D009994:Osmolar Concentration; D010196:Pancreatic Elastase / Q000378:metabolism; D014132:Trachea / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000941:Antigens; C071244:N-(9H-(2,7-dimethylfluoren-9-ylmethoxy)carbonyl)leucine; D009113:Muramidase; D010196:Pancreatic Elastase; D007930:Leucine