Dataset Information

The anti-parasitic drug miltefosine suppresses activation of human eosinophils and ameliorates allergic inflammation in mice.

ABSTRACT:

Background and purpose

Miltefosine is an alkylphosphocholine drug with proven effectiveness against various types of parasites and cancer cells. Miltefosine is not only able to induce direct parasite killing but also modulates host immunity, for example by reducing the severity of allergies in patients. To date, there are no reports on the effect of miltefosine on eosinophils, central effector cells involved in allergic inflammation.

Experimental approach

We tested the effect of miltefosine on the activation of human eosinophils and their effector responses in vitro and in mouse models of eosinophilic migration and ovalbumin-induced allergic lung inflammation.

Key results

The addition of miltefosine suppressed several eosinophilic effector reactions such as CD11b up-regulation, degranulation, chemotaxis and downstream signalling. Miltefosine significantly reduced the infiltration of immune cells into the respiratory tract of mice in an allergic cell recruitment model. Finally, in a model of allergic inflammation, treatment with miltefosine resulted in an improvement of lung function parameters.

Conclusion and implications

Our observations suggest a strong modulatory activity of miltefosine in the regulation of eosinophilic inflammation in vitro and in vivo. Our data underline the potential efficacy of miltefosine in the treatment of allergic diseases and other eosinophil-associated disorders and may raise important questions regarding the immunomodulatory effect of miltefosine in patients treated for leishmania infections.

SUBMITTER: Knuplez E

PROVIDER: S-EPMC9328393 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

The anti-parasitic drug miltefosine suppresses activation of human eosinophils and ameliorates allergic inflammation in mice.

Knuplez Eva E Kienzl Melanie M Trakaki Athina A Schicho Rudolf R Heinemann Akos A Sturm Eva M EM Marsche Gunther G

British journal of pharmacology 20210202 5

<h4>Background and purpose</h4>Miltefosine is an alkylphosphocholine drug with proven effectiveness against various types of parasites and cancer cells. Miltefosine is not only able to induce direct parasite killing but also modulates host immunity, for example by reducing the severity of allergies in patients. To date, there are no reports on the effect of miltefosine on eosinophils, central effector cells involved in allergic inflammation.<h4>Experimental approach</h4>We tested the effect of m ...[more]

PMID: 33450054

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Project description:BackgroundThe recruitment of CD4+CD25+Foxp3+T (Treg) cells is one of the most important mechanisms by which parasites down-regulate the immune system.Methodology/principal findingsWe compared the effects of Treg cells from Trichinella spiralis-infected mice and uninfected mice on experimental allergic airway inflammation in order to understand the functions of parasite-induced Treg cells. After four weeks of T. spiralis infection, we isolated Foxp3-GFP-expressing cells from transgenic mice using a cell sorter. We injected CD4+Foxp3+ cells from T. spiralis-infected [Inf(+)Foxp3+] or uninfected [Inf(-)Foxp3+] mice into the tail veins of C57BL/6 mice before the induction of inflammation or during inflammation. Inflammation was induced by ovalbumin (OVA)-alum sensitization and OVA challenge. The concentrations of the Th2-related cytokines IL-4, IL-5, and IL-13 in the bronchial alveolar lavage fluid and the levels of OVA-specific IgE and IgG1 in the serum were lower in mice that received intravenous application of Inf(+)Foxp3+ cells [IV(inf):+(+) group] than in control mice. Some features of allergic airway inflammation were ameliorated by the intravenous application of Inf(-)Foxp3+ cells [IV(inf):+(-) group], but the effects were less distinct than those observed in the IV(inf):+(+) group. We found that Inf(+)Foxp3+ cells migrated to inflammation sites in the lung and expressed higher levels of Treg-cell homing receptors (CCR5 and CCR9) and activation markers (Klrg1, Capg, GARP, Gzmb, OX40) than did Inf(-)Foxp3+ cells.Conclusion/significanceT. spiralis infection promotes the proliferation and functional activation of Treg cells. Parasite-induced Treg cells migrate to the inflammation site and suppress immune responses more effectively than non-parasite-induced Treg cells. The adoptive transfer of Inf(+)Foxp3+ cells is an effective method for the treatment and prevention of allergic airway diseases in mice and is a promising therapeutic approach for the treatment of allergic airway diseases.

Dataset Information

The anti-parasitic drug miltefosine suppresses activation of human eosinophils and ameliorates allergic inflammation in mice.

Background and purpose

Experimental approach

Key results

Conclusion and implications

Publications

The anti-parasitic drug miltefosine suppresses activation of human eosinophils and ameliorates allergic inflammation in mice.

Similar Datasets

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