Topical FK506: suppression of allergic and irritant contact dermatitis in the guinea pig

Lauerma, Antti; Stein, Beth; Homey, Bernhard; Lee, C. H.; Bloom, Ernest; Maibach, Howard I.

doi:10.1007/bf00402225

Cited by 50 publications

(19 citation statements)

References 22 publications

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“…The structure and barrier properties of the skin in man are well known to resemble those in guinea pigs more than those in mice. In addition, guinea pigs are reported to be relatively resistant to steroids [11], and, except for steroids and some immunosuppressive agents such as cyclosporin A [12, 13]and FK-506 [14], few compounds are known to have suppressive effects against CHR in guinea pigs by topical application [15]. Taken together, the data would suggest CX-659S to be an effective topical drug for the treatment of cutaneous disorders in humans.…”

Section: Discussionmentioning

confidence: 85%

Suppressive Effect of Topically Applied CX-659S, a Novel Diaminouracil Derivative, on the Contact Hypersensitivity Reaction in Various Animal Models

Goto

Inoue

Tsuchiya

et al. 2000

Int Arch Allergy Immunol

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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.

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Section: Discussionmentioning

confidence: 85%

Suppressive Effect of Topically Applied CX-659S, a Novel Diaminouracil Derivative, on the Contact Hypersensitivity Reaction in Various Animal Models

Goto

Inoue

Tsuchiya

et al. 2000

Int Arch Allergy Immunol

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“…Allergic contact dermatitis is responsive to topical FK-506 as well. The efficacy in this condition was reported in humans [21] and further investigated in guinea pig [22]. Whether topical FK-506 is also effective in psoriasis vulgaris remains to be verified.…”

Section: Clinical Application In Dermatologymentioning

confidence: 91%

FK-506/Tacrolimus

Wollenberg¹,

Bieber²

1997

Strategies for Immunointerventions in Dermatology

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“…Animal model studies (guinea pigs and pigs) have shown topical tacrolimus to be effective in the prevention and the treatment of acute allergic and irritant contact dermatitis. 16,17 In a human study, topical tacrolimus (at concentrations of 0.01%, 0.1%, and 1%) in ethanol and ethanol alone were applied to 5 volunteers for 48 hours. 1-Chloro-2,4-dinitrobenzene (DNCB) was then applied to the skin.…”

Section: Acute Contact Dermatitismentioning

confidence: 99%