Effects of NZ-107 on airway inflammation and cell activation in guinea-pigs.
The effects of NZ-107 on some airway inflammation models and the generation of superoxide anion (O2-) were studied in guinea-pigs. Airway inflammation was caused by intra-tracheal injection of murine recombinant interleukin-5 (mrIL-5, 15 micrograms/animal), inhalation of platelet-activating factor (PAF, 0.003%) and intra-tracheal injection of leukotriene B4 (LTB4, 10 micrograms/animal). NZ-107 (4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone) at a dose of 50 mg kg-1, intraperitoneally reduced mrIL-5- and PAF-induced eosinophilia. This compound at a dose of 25 and 50 mg kg-1 also suppressed LTB4-induced eosinophilia and neutrophilia in bronchoalveolar lavage fluid (BALF). On the other hand, prednisolone at a dose of 20 mg kg-1, i.p., prevented the increased number of macrophages, eosinophils and neutrophils induced by mrIL-5, the increased number of eosinophils induced by PAF and the increased number of eosinophils and neutrophils induced by LTB4 in BALF. Furthermore, both drugs reduced mrIL-5- or PAF-induced increase in the number of airway epithelial cells in BALF. The generation of O2- was measured by the method of cytochrome C reduction. NZ-107 (10-100 micrograms mL-1) attenuated PAF- and FMLP-induced O2- production from macrophages and reduced PAF-induced O2- generation by eosinophils but had no effect on that from neutrophils. These results indicate that NZ-107 prevents the increased number of pulmonary eosinophils and airway epithelial cells and the activation of macrophages and eosinophils, suggesting that NZ-107 may be useful as a remedy for airway inflammatory diseases such as bronchial asthma.
Iwama
T
T
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Nagai
H
H
Koda
A
A
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D002452:Cell Count / Q000187:drug effects; D004804:Eosinophils / Q000187:drug effects; D006168:Guinea Pigs; D015848:Interleukin-5 / Q000633:toxicity; D007962:Leukocytes / Q000187:drug effects*; D020024:Leukotriene Antagonists; D007975:Leukotriene B4 / Q000633:toxicity; D008214:Lymphocytes / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000187:drug effects*; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D010972:Platelet Activating Factor / Q000633:toxicity; D011239:Prednisolone / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology* / Q000627:therapeutic use; D013481:Superoxides / Q000378:metabolism
D015848:Interleukin-5; D020024:Leukotriene Antagonists; D010972:Platelet Activating Factor; D011724:Pyridazines; C062698:NZ 107; D013481:Superoxides; D007975:Leukotriene B4; D011239:Prednisolone