Effects of the phosphodiesterase 4 inhibitors SB 207499 and AWD 12-281 on the inflammatory reaction in a model of allergic dermatitis.

Abstract

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.

• Authors: Wolfgang Bäumer, Gilbert Gorr, Joachim Hoppmann, Andreas M Ehinger, Britt Ehinger, Manfred Kietzmann
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 446 Issue 1-3 Pg. 195-200 (Jun 20 2002) ISSN: 0014-2999 [Print] Netherlands
• PMID: 12098602 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AWD 12-281
• Amides
• Cyclohexanecarboxylic Acids
• Indoles
• Interleukin-1
• Nitriles
• Phosphodiesterase Inhibitors
• Toluene 2,4-Diisocyanate
• Interleukin-4
• Immunoglobulin E
• Cilomilast
• 3',5'-Cyclic-AMP Phosphodiesterases
• Cyclic Nucleotide Phosphodiesterases, Type 4

Topics

• 3',5'-Cyclic-AMP Phosphodiesterases (antagonists & inhibitors)
• Amides (pharmacology)
• Animals
• Cyclic Nucleotide Phosphodiesterases, Type 4
• Cyclohexanecarboxylic Acids (pharmacology)
• Dermatitis, Allergic Contact (etiology, metabolism)
• Ear (pathology)
• Edema (pathology)
• Immunoglobulin E (metabolism)
• Indoles (pharmacology)
• Interleukin-1 (metabolism)
• Interleukin-4 (metabolism)
• Mice
• Mice, Inbred BALB C
• Nitriles
• Phosphodiesterase Inhibitors (pharmacology)
• Skin (metabolism)
• Time Factors
• Toluene 2,4-Diisocyanate