کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2533827 | 1559065 | 2010 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: The putative lipid raft modulator miltefosine displays immunomodulatory action in T-cell dependent dermal inflammation models The putative lipid raft modulator miltefosine displays immunomodulatory action in T-cell dependent dermal inflammation models](/preview/png/2533827.png)
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 (20 µM) 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 100 mg/kg p.o. (P < 0.01). The ear tissue content of the cytokines IL1ß, IL4 and IL6 was also reduced reaching 56% or 52% reduction of IL1ß (P < 0.01) after 2% topical or 100 mg/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 100 mg/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.
Journal: European Journal of Pharmacology - Volume 628, Issues 1–3, 25 February 2010, Pages 226–232