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Miltefosine suppresses inflammation in a mouse model of inflammatory bowel disease
Auke P Verhaar1, Manon E Wildenberg, Anje A te Velde
1Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, the Netherlands.
Background:
The repertoire of immunomodulators that can be used for the treatment of inflammatory bowel disease is limited. The use of these drugs is further restricted by the occurrence of side effects in a proportion of patients. Miltefosine (hexadecylphosphocholine) is a lipid drug developed in the 1980s for the treatment of cancer but is nowadays best known for its application in the oral treatment of leishmaniasis. Although the exact mechanism of action of miltefosine has yet to be elucidated, the drug has previously been shown to inhibit phospholipases and protein kinase C, both key components of proproliferative signal transduction in T cells.
Methods:
Stimulated peripheral blood lymphocyte were treated with miltefosine, and proliferation was measured. We use the CD45RB T-cell transfer colitis model to investigate the effect of miltefosine treatment on intestinal inflammation. Effects on the severity of colitis were studied by histochemical and immunohistochemical staining, and cytokine levels were determined using a cytokine bead array.
Results:
Miltefosine inhibited T-cell proliferation in vitro. In the transfer model, miltefosine significantly ameliorated the severity of colitis as measured by clinical, (immuno)histochemical, and biochemical parameters.
Conclusions:
Miltefosine inhibits T-cell proliferation and effectively reduces inflammation in the T-cell transfer model. The drug may therefore be a candidate immunomodulator for inflammatory bowel disease.
Insights
Miltefosine, a lipid drug, inhibits T-cell proliferation and reduces intestinal inflammation in a colitis model. This suggests its potential as an immunomodulator for inflammatory bowel disease treatment.
Area of Science:
- Immunology
- Pharmacology
- Gastroenterology
Background:
- Limited immunomodulators exist for inflammatory bowel disease (IBD), with side effects restricting use.
- Miltefosine (hexadecylphosphocholine) is a lipid drug with known anticancer and antileishmanial applications.
- Miltefosine may inhibit T-cell signaling pathways, including phospholipases and protein kinase C.
Purpose of the Study:
- To investigate the effect of miltefosine on T-cell proliferation.
- To evaluate miltefosine's efficacy in reducing intestinal inflammation using a T-cell transfer colitis model.
Main Methods:
- In vitro treatment of lymphocytes with miltefosine to measure proliferation.
- Utilizing the CD45RB T-cell transfer colitis model in mice.
- Assessing colitis severity via clinical, histochemical, and biochemical parameters, including cytokine levels.
Main Results:
- Miltefosine demonstrated significant inhibition of T-cell proliferation in vitro.
- Miltefosine treatment markedly reduced the severity of colitis in the transfer model.
- Clinical, histochemical, and biochemical markers of inflammation were significantly improved.
Conclusions:
- Miltefosine effectively inhibits T-cell proliferation.
- Miltefosine shows therapeutic potential for reducing inflammation in experimental colitis.
- Miltefosine is a promising candidate for treating inflammatory bowel disease.
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