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Suppressive Effect of Topically Applied CX-659S, a Novel Diaminouracil Derivative, on the Contact Hypersensitivity Reaction in Various Animal Models.
- Source :
-
International Archives of Allergy & Immunology . 2000, Vol. 123 Issue 4, p341-348. 8p. - Publication Year :
- 2000
-
Abstract
- Background: The T-cell-mediated contact hypersensitivity reaction (CHR) is thought to be involved in the pathogenesis of clinical cutaneous disorders including atopic dermatitis. A novel diaminouracil derivative, CX-659S, has been reported to have an inhibitory activity against picryl chloride (PC)-induced CHR when administered either orally or percutaneously. The inhibitory effect of topical CX-659S was assessed in three CHR models in the present study. In addition, to elucidate the mechanism of action of this compound, we examined the effect of CX-659S on the expression of messenger RNAs for proinflammatory cytokines after elicitation in PC models. Methods: For the in vivo evaluation of the efficacy of CX-659S, we used PC- or oxazolone-induced CHR in mice and 2,4-dinitrochlorobenzene (DNCB)-induced CHR in guinea pigs. CX-659S was topically applied immediately after the hapten challenge in each model. To assess the effect on gene expression of cytokines, we used the reverse transcriptase-polymerase chain reaction (RT-PCR), a semiquantitative technique with specific primers. Results: Topical CX-659S dose-dependently inhibited ear swelling at 24 h after the challenge in the two mouse models. This inhibitory effect was histologically confirmed in the PC model. Topically applied CX-659S also inhibited erythema and edema formation 24 h after challenge in the guinea pig model. CX-659S inhibited the expression of mRNA for proinflammatory cytokines IL-1β and TNF-α in vivo. Conclusions: Topically applied CX-659S showed significant inhibitory activities against CHR models both in mice and in guinea pigs. Inhibition profiles of CX-659S toward mRNA expression for proinflammatory cytokines corroborated these findings. CX-659S thus could be a useful therapeutic agent for allergic cutaneous disorders such as allergic contact dermatitis and atopic dermatitis.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10182438
- Volume :
- 123
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- International Archives of Allergy & Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 11335223
- Full Text :
- https://doi.org/10.1159/000053647