Bäumer Wolfgang, Gorr Gilbert, Hoppmann Joachim, Ehinger Andreas M, Ehinger Britt, Kietzmann Manfred
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Buenteweg 17, 30559, Hanover, Germany.
Eur J Pharmacol. 2002 Jun 20;446(1-3):195-200. doi: 10.1016/s0014-2999(02)01810-1.
The inhibitors of the phosphodiesterase 4, SB 207499 (cilomilast, c-4-cyano-4-(3-cyclopentyloxy-4-methoxy-phenyl)-r-L-cyclohexane carboxylic acid) and AWD 12-281 (N-(3,5-dichloropyrid-4-yl)-[1-(4-fluorobenzyl)-5-hydroxy-indole-3-yl]-glyoxylic acid amide) were tested in a model of allergic dermatitis in mice. To obtain an allergic dermatitis, BALB/c mice were sensitized to toluene-2,4-diisocyanate. The allergic reaction was challenged by topical administration of toluene-2,4-diisocyanate onto the mice ears. Before challenge, two groups of mice were treated topically (ear skin) with SB 207499 or AWD 12-281. There was a significant ear swelling in toluene-2,4-diisocyanate-challenged mice ears 4, 8, 16, 24 and 48 h after challenge. SB 207499 and AWD 12-281 inhibited this swelling significantly 8, 16, 24 and 48 h after the challenge. For biochemical parameters and histology, ears were sampled from mice sacrificed 4, 8 and 16 h after the challenge. In homogenized tissue, SB 207499 and AWD 12-281 inhibited significantly the secretion of interleukin 1beta induced by toluene-2,4-diisocyanate 4 and 8 h after challenge. The cell influx (granulocytes) observed in the toluene-2,4-diisocyanate-challenged mice 8 and 16 h after challenge was nearly abolished by AWD 12-281 and SB 204799.
磷酸二酯酶4抑制剂SB 207499（西洛司特，c-4-氰基-4-(3-环戊氧基-4-甲氧基苯基)-r-L-环己烷羧酸）和AWD 12-281（N-(3,5-二氯吡啶-4-基)-[1-(4-氟苄基)-5-羟基吲哚-3-基]-乙醛酸酰胺）在小鼠过敏性皮炎模型中进行了测试。为诱导过敏性皮炎，将BALB/c小鼠用甲苯-2,4-二异氰酸酯致敏。通过将甲苯-2,4-二异氰酸酯局部涂抹于小鼠耳部来激发过敏反应。在激发前，两组小鼠分别用SB 207499或AWD 12-281进行局部（耳部皮肤）治疗。在激发后4、8、16、24和48小时，甲苯-2,4-二异氰酸酯激发的小鼠耳部出现明显的耳部肿胀。SB 207499和AWD 12-281在激发后8、16、24和48小时显著抑制了这种肿胀。为检测生化参数和组织学情况，在激发后4、8和16小时处死小鼠并采集耳部样本。在匀浆组织中，SB 207499和AWD 12-281在激发后4和8小时显著抑制了甲苯-2,4-二异氰酸酯诱导的白细胞介素1β分泌。在激发后8和16小时，AWD 12-281和SB 204799几乎消除了在甲苯-2,4-二异氰酸酯激发的小鼠中观察到的细胞内流（粒细胞）。
