T. Iwama et al., EFFECTS OF NZ-107 ON AIRWAY INFLAMMATION AND CELL ACTIVATION IN GUINEA-PIGS, Journal of Pharmacy and Pharmacology, 45(4), 1993, pp. 286-291
The effects of NZ- 107 on some airway inflammation models and the gene
ration of superoxide anion (O2-) Were studied in guinea-pigs. Airway i
nflammation was caused by intra-tracheal injection of murine recombina
nt interleukin-5 (mrIL-5, 15 mug/animal), inhalation of platelet-activ
ating factor (PAF, 0.003%) and intra-tracheal injection of leukotriene
B4 (LTB4, 10 mug/animal). NZ-107 -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 macro
phages, eosinophils and neutrophils induced by mrIL-5, the increased n
umber of eosinophils induced by PAF and the increased number of eosino
phils and neutrophils induced by LTB, in BALF. Furthermore, both drugs
reduced mrIL-5- or PAF-induced increase in the number of airway epith
elial cells in BALF. The generation of O2- was measured by the method
of cytochrome C reduction. NZ-107 (10-100 mug mL-1) attenuated PAF- an
d FMLP-induced O2- production from macrophages and reduced PAF-induced
02- generation by eosinophils but had no effect on that from neutroph
ils. These results indicate that NZ-107 prevents the increased number
of pulmonary eosinophils and airway epithelial cells and the activatio
n of macrophages and cosinophils, suggesting that NZ-107 may be useful
as a remedy for airway inflammatory diseases such as bronchial asthma
.