Effects of the phosphodiesterase 4 inhibitors SB 207499 and AWD 12-281 on the inflammatory reaction in a model of allergic dermatitis.
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.
Bäumer
Wolfgang
W
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Buenteweg 17, 30559, Hanover, Germany. wolfgang.baeumer@tiho-hannover.de
Gorr
Gilbert
G
Hoppmann
Joachim
J
Ehinger
Andreas M
AM
Ehinger
Britt
B
Kietzmann
Manfred
M
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000577:Amides / Q000494:pharmacology*; D000818:Animals; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D017449:Dermatitis, Allergic Contact / Q000209:etiology / Q000378:metabolism*; D004423:Ear / Q000473:pathology; D004487:Edema / Q000473:pathology; D007073:Immunoglobulin E / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D007375:Interleukin-1 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009570:Nitriles; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D012867:Skin / Q000378:metabolism; D013997:Time Factors; D014051:Toluene 2,4-Diisocyanate
C470045:AWD 12-281; D000577:Amides; D003509:Cyclohexanecarboxylic Acids; D007211:Indoles; D007375:Interleukin-1; D009570:Nitriles; D010726:Phosphodiesterase Inhibitors; D014051:Toluene 2,4-Diisocyanate; D015847:Interleukin-4; D007073:Immunoglobulin E; C433247:Cilomilast; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4