| The putative lipid raft modulator miltefosine displays immunomodulatory action in T-cell dependent dermal inflammation models. | |
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MedLine Citation:
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PMID: 19917276 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Miltefosine is currently marketed for treatment of skin metastasis of breast cancer and leishmaniasis. The mechanism of action is not fully understood, however, miltefosine is considered to be a prototype lipid raft modulator. The compound was shown to inhibit anti-IgE induced histamine release from human skin mast cells. After topical treatment it reduced skin reaction in allergic human volunteers undergoing a skin prick test. The aim of this study was to test whether miltefosine could also modify T-cell signalling and whether the drug may be useful for the treatment of atopic dermatitis. Miltefosine (20microM) inhibited T-cell proliferation by >50% in the mixed leukocyte test. In the toluene diisocyanate induced ear swelling test, miltefosine, administered topically as 2 and 6% solution or orally, attenuated ear swelling reaching 70% of the effect of dexamethasone at 100mg/kg p.o. (P<0.01). The ear tissue content of the cytokines IL1beta, IL4 and IL6 was also reduced reaching 56% or 52% reduction of IL1beta (P<0.01) after 2% topical or 100mg/kg p.o. Miltefosine significantly attenuated the allergic sensitization in the model of ovalbumin induced delayed-type hypersensitivity in mice. In a model of toluene diisocyanate induced scratching a significant (P=0.0047) reduction of scratching from 47 to 6 bouts was achieved with 100mg/kg p.o. The data indicate that miltefosine modulates T-cell function in models for Th1 and Th2 related activity. This profile opens up the possibility for the treatment of T-cell related allergic diseases with a novel class of lipid raft modulator drugs such as miltefosine. |
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Authors:
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Wolfgang B?umer; Piotr Wla?; Gary Jennings; Chris Rundfeldt |
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Publication Detail:
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Type: Journal Article Date: 2009-11-14 |
Journal Detail:
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Title: European journal of pharmacology Volume: 628 ISSN: 1879-0712 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-01-27 Completed Date: 2010-04-05 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 226-32 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Administration, Topical Animals Anti-Inflammatory Agents / administration & dosage, immunology, pharmacology, therapeutic use Arachidonic Acid / pharmacology Disease Models, Animal Ear / pathology Female Hypersensitivity / immunology Immunologic Factors / administration & dosage, immunology, pharmacology, therapeutic use Inflammation / chemically induced, drug therapy, immunology*, metabolism Interleukins / metabolism Membrane Microdomains / drug effects* Mice Phosphorylcholine / administration & dosage, analogs & derivatives*, immunology, pharmacology, therapeutic use Pruritus / drug therapy, immunology Skin / drug effects, immunology, pathology* T-Lymphocytes / immunology* Toluene 2,4-Diisocyanate / immunology |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents; 0/Immunologic Factors; 0/Interleukins; 107-73-3/Phosphorylcholine; 506-32-1/Arachidonic Acid; 58066-85-6/miltefosine; 584-84-9/Toluene 2,4-Diisocyanate |
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