Miltefosine Inhibits Human Mast Cell Activation and Mediator Release Both In Vitro and In Vivo

Weller, Karsten; Artuc, Metin; Jennings, Gary; Friedrichson, Tim; Guhl, Sven; Santos, R. Vieira dos; Sünder, Cathleen Annett; Zuberbier, Torsten; Maurer, Marcus

doi:10.1038/jid.2008.248

Cited by 27 publications

(36 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is possible that miltefosine improved phagocytosis through the increment in fluidity of the membrane of the macrophage that occurs by the inhibition of the de novo synthesis of phosphatidylcholine, a major component of biological membranes [32], consequently improving chemotaxis, motility, adherence of the macrophage and phagocytosis [20,22,[33][34][35][36][37][38]. Our data agree with the enhanced phagocytosis of L. donovani by macrophages of hamsters treated per os with miltefosine for 5 days [39].…”

Section: Discussionsupporting

confidence: 93%

Miltefosine enhances phagocytosis but decreases nitric oxide production by peritoneal macrophages of C57BL/6 mice

Ponte

Alves

Sampaio

et al. 2012

International Immunopharmacology

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 93%

Miltefosine enhances phagocytosis but decreases nitric oxide production by peritoneal macrophages of C57BL/6 mice

Ponte

Alves

Sampaio

et al. 2012

International Immunopharmacology

View full text Add to dashboard Cite

“…Weller et al, in 2009, demonstrated that processes mediated by signal transduction receptors, such as those involved in immunoglobulin E (IgE) -receptor (FceRI) mast cell-dependent activation with subsequent degranulation, are regulated by lipid rafts in the cell membrane (145). The same study also showed that miltefosine can inhibit the activation of degranulation and inflammatory mediator release by human mast cells in vitro, being able to avoid inflammatory reactions mediated by these cells.…”

Section: Chronic Spontaneous Urticariamentioning

confidence: 58%

Alkylphospholipids – A Promising Class of Chemotherapeutic Agents with a Broad Pharmacological Spectrum

et al. 2013

View full text Add to dashboard Cite

-PURPOSE:Since when alkylphospholipds (ALPs) were discovered and, even further after miltefosine's approval for the treatment of cutaneous metastasis of breast cancer and leishmaniasis, their activity against many other diseases have been extensively studied. This review aims to provide a summary of the alkylphospholipids' applications investigated so far. RESULTS: The mechanism of action of ALPs is not fully understood, however it is believed that they interfere with lipid homeostasis leading to cell apoptosis. Due to ALPs cytotoxic activity, this class of molecules has shown to be effective against many diseases and conditions. Besides the approval of miltefosine for application in cutaneous metastasis of breast cancer and visceral and cutaneous leishmaniasis, several other analogs have proved efficacy and are promising as less toxic alternatives. ALPs have also shown in vitro and in vivo activity against Trypanosoma spp., amoebae, Tricomonas vaginalis, Schistosoma mansoni, HIV, and some fungi and bacteria species. The use of ALPs for intraocular lens coating is also under investigation. In addition, a clinical trial comparing miltefosine with usual treatments to spontaneous urticaria is also being conducted. CONCLUSIONS: Alkylphospholipids present such a broad pharmacological spectrum that justifies the need for further investigations of the drug class mechanisms of action, as well as the search for new analogs with improved activity and toxicological profiles.

show abstract

“…Miltefosine was also shown to inhibit histamine release in human mast cells (Weller et al, 2009;Batista et al, 2010Batista et al, , 2011. Ten minutes of pretreatment with 25 mM miltefosine reduced anti-IgE-induced histamine release by more than 50%.…”

Section: Miltefosine and Allergic Diseasementioning

confidence: 99%

“…The effect of miltefosine on membrane integrity could also explain why mast cells are inhibited in their IgE-dependent histamine release. Upon activation, IgE receptors cluster in organized microdomains (Weller et al, 2009;Silveira E Souza et al, 2011). Likewise, T-cell activation is dependent on the formation and organization of T-cell receptor microclusters and formation of the immunologic synapse (Kabouridis and Jury, 2008).…”

Section: Mechanism Of Actionmentioning

confidence: 99%

See 1 more Smart Citation

Repurposing Miltefosine for the Treatment of Immune-Mediated Disease?

Verhaar

Wildenberg

Peppelenbosch

et al. 2014

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Miltefosine is an ether lipid that was initially developed for cancer treatment in the early 1980s. Miltefosine largely failed development for oncology, although it was approved for the topical treatment of breast cancer metastasis. It was subsequently discovered that miltefosine is a highly effective treatment of visceral Leishmaniasis, a parasitic disease that affects millions worldwide and causes an estimated 30,000 fatalities each year. Oral treatment with miltefosine is generally well tolerated and has relatively few adverse effects. The exact mechanism of action of miltefosine treatment is still under investigation. Its close resemblance to phospholipids allows it to be quickly taken up by cell membranes and affect related processes, such as lipid metabolism and signaling through lipid rafts. These processes play an important role in the immune response and it comes as no surprise that miltefosine has been successfully tested for the treatment of a number of immune-mediated diseases in preclinical models of disease. Drug repurposing of miltefosine for immunemediated diseases may provide an opportunity to expand the limited number of drugs that are currently available for therapeutic use.

show abstract

Miltefosine Inhibits Human Mast Cell Activation and Mediator Release Both In Vitro and In Vivo

Cited by 27 publications

References 15 publications

Miltefosine enhances phagocytosis but decreases nitric oxide production by peritoneal macrophages of C57BL/6 mice

Miltefosine enhances phagocytosis but decreases nitric oxide production by peritoneal macrophages of C57BL/6 mice

Alkylphospholipids – A Promising Class of Chemotherapeutic Agents with a Broad Pharmacological Spectrum

Repurposing Miltefosine for the Treatment of Immune-Mediated Disease?

Contact Info

Product

Resources

About