Immunobiology of Cyclosporin A—a Review

Thomson, A. W.

doi:10.1038/icb.1983.14

Cited by 67 publications

(28 citation statements)

References 12 publications

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“…Although pri marily used for prophylaxis and treatment of organ rejection, oral or intramuscular ad ministration of CSA has proven useful in treating psoriasis [1,2], When systemic routes of administration are used to deliver drugs to specific extravascular sites, suffi cient drug has to be administered to account for dilution of the drug due to its distribu-tion through all tissues of the body. With respect to CSA, systemic regimens required to suppress skin symptomatology often re sult in adverse side effects [3], Moreover, systemic administration still may not over come the inaccessibility of the skin tissue to the drug. In these regards, 'drug delivery* may be the singularly most limiting factor in the effective treatment of psoriasis with CSA.…”

Section: Introductionmentioning

confidence: 99%

Topical Delivery of Ciclosporin: Evaluation of Various Formulations Using in vitro Diffusion Studies in Hairless Mouse Skin

Egbaria

Ramachandran

Weiner

1990

Skin Pharmacol Physiol

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The kinetics and extent of uptake of ciclosporin in various strata of hairless mouse skin upon topical application of several ciclosporin formulations were determined by in vitro diffusion cell experiments. The ciclosporin formulations tested included a hydroalcoholic solution, an oil-in-water emulsion and two liposomal systems. The accumulation of drug in stratum corneum is in the order: ‘skin lipid’ liposomes > ‘phospholipid’ liposomes > emulsion > hydroalcoholic solution. The total combined amount of drug in the deeper skin strata and the receiver compartment followed the order: hydroalcoholic solution > > ‘phospholipid’ liposomes > ‘skin lipid’ liposomes > emulsion. The results suggest that topically applied liposomes, particularly those prepared from lipid mixutres having compositions similar to the stratum corneum, may provide sustained, enhanced levels of ciclosporin in the stratum corneum (the reservoir) while minimizing high levels in strata associated with blood and lymph supplies.

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Section: Introductionmentioning

confidence: 99%

Topical Delivery of Ciclosporin: Evaluation of Various Formulations Using in vitro Diffusion Studies in Hairless Mouse Skin

Egbaria

Ramachandran

Weiner

1990

Skin Pharmacol Physiol

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“…Cyclosporine A (CsA), a potent immunosuppres sive drug, has been shown to prolong allograft sur vival in man and other mammals [1,2] and to block T cell-mediated responses such as allograft rejection, delayed-type hypersensitivity (DTH) reactions and in vitro cytotoxicity [1,3,4]. Our studies have shown that CsA treatment abrogates DTH [5] and the cell transfer studies reported here were carried out to identify and characterise the cells involved in CsA-induced sup pression of DTH to alloantigens.…”

mentioning

confidence: 99%

Characterisation of Cyclosporine-Induced Suppressor Cells in Murine Delayed-Type Hypersensitivity Responses

Mirisklavos¹,

Mottram²,

Dumble³

et al. 1986

Int Arch Allergy Immunol

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The effect of Cyclosporine A (CsA) on T cell-mediated delayed-type hypersensitivity (DTH) reactions to murine alloantigens was analysed by transferring spleen cells from sensitised and suppressed mice into irradiated naive recipients. Selective removal of Thy1+, Ly1+ or Ly2+ cells prior to intravenous transfer of cells from alloantigen-sensitised mice showed that Ly1+ Thy1+ cells transferred sensitivity. Concomitant treatment of mice with alloantigen and CsA suppressed the DTH response to alloantigens, and spleen cells transferred from these suppressed mice abrogated the response of sensitised cells transferred at the same time. The suppressor cells were strain-restricted and antigen-specific with the surface phenotype Thy + , Ly1–– Ly2+.

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“…According to the results presented here, CsA-sensitive p i00 phosphorylation shows the following characteristics: ( 1 ) it occurs not only in epidermis but -much more pro nounced -also in other tissues such as pan creas and reticulocytes, (2) it is catalyzed by a Ca2+/CaM-dependent protein kinase rather than by protein kinase C, the endoge nous phorbol ester receptor, (3) it exhibits a rather short metabolic half-life of 1.5 h being probably due to a rapid turnover of the pi00-kinase and (4) the p i00 substrate pro tein is identical with EF-2 of ribosomal pro tein synthesis.…”

Section: Discussionmentioning

confidence: 99%

Ciclosporin Inhibits Phorbol-Ester-Induced Hyperplastic Transformation and Tumor Promotion in Mouse Skin Probably by Suppression of Ca<sup>2+</sup>/Calmodulin-Dependent Processes such as Phosphorylation of Elongation Factor 2

Gschwendt¹,

Kittstein²,

Marks³

1988

Skin Pharmacol Physiol

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This study deals with the mechanism of the inhibitory effect exerted by the immunosuppressant ciclosporin (CsA) on phorbol-ester-induced inflammation, epidermal hyperplasia and tumor promotion in mouse skin in vivo. This effect coincides with an inhibition of the phosphorylation of a 100-kilodalton protein (p 100) in epidermal cytosol in vitro, which has been identified as elongation factor 2 (EF-2) of protein biosynthesis. Phosphorylation of EF-2 is dependent on Ca²⁺ and calmodulin, and inhibition of EF-2 phosphorylation by CsA is due to an interaction of CsA with calmodulin. The EF-2 phosphorylation system has a metabolic half-life of 1.5 h probably due to a rather rapid turnover rate of the EF-2 kinase. Since CsA inhibits specifically 12–0-tetradecanoylphorbol-13-acetate (TPA)-stimulated but not basal protein synthesis in epidermis, it is proposed that Ca²⁺/calmodulin-dependent phosphorylation of EF-2 is involved in the induction of the hyperplastic response by TPA and that CsA suppresses TPA effects by inhibition of EF-2-phosphorylation and perhaps other calmodulin-dependent processes. The potential applicability of calmodulin inhibitors in the treatment of hyperproliferative skin diseases is discussed.

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Immunobiology of Cyclosporin A—a Review

Cited by 67 publications

References 12 publications

Topical Delivery of Ciclosporin: Evaluation of Various Formulations Using in vitro Diffusion Studies in Hairless Mouse Skin

Topical Delivery of Ciclosporin: Evaluation of Various Formulations Using in vitro Diffusion Studies in Hairless Mouse Skin

Characterisation of Cyclosporine-Induced Suppressor Cells in Murine Delayed-Type Hypersensitivity Responses

Ciclosporin Inhibits Phorbol-Ester-Induced Hyperplastic Transformation and Tumor Promotion in Mouse Skin Probably by Suppression of Ca<sup>2+</sup>/Calmodulin-Dependent Processes such as Phosphorylation of Elongation Factor 2

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