The putative lipid raft modulator miltefosine displays immunomodulatory action in T-cell dependent dermal inflammation models

European Journal of Pharmacology
Wolfgang BäumerChris Rundfeldt

Abstract

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...Continue Reading

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Citations

Jul 3, 2013·Inflammatory Bowel Diseases·Auke P VerhaarGijs R van den Brink
Aug 15, 2014·Naunyn-Schmiedeberg's Archives of Pharmacology·S SchumacherW Bäumer
Mar 5, 2013·Journal of Pharmaceutical Sciences·Rodrigo Alves MoreiraAntonio Alonso
Mar 1, 2012·Acta histochemica·Alexandra Paiva AraújoSelma Giorgio
Mar 6, 2012·The Journal of Dermatological Treatment·Marcus MaurerFrank Siebenhaar
Oct 27, 2016·Nature Reviews. Immunology·Wei WuChenqi Xu
Jan 4, 2013·Innate Immunity·Tina BaslerWolfgang Bäumer
May 31, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Risako Tajiki-NishinoTomoki Fukuyama
May 1, 2019·Antimicrobial Agents and Chemotherapy·Semra PalićThomas P C Dorlo
May 6, 2019·International Journal of Molecular Sciences·Doralicia CasaresCatalina Ana Rosselló
May 17, 2014·The Journal of Pharmacology and Experimental Therapeutics·Auke P VerhaarGijs R van den Brink
Mar 7, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sonia AndréJérôme Estaquier
Apr 23, 2017·International Immunopharmacology·Yinhuan LiChenghua He
Oct 26, 2021·International Journal of Antimicrobial Agents·Semra PalićThomas P C Dorlo

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