期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 110, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.intimp.2022.108952
关键词
Human visceral leishmaniasis; Pamidronate; Immunomodulation; Drug repositioning
资金
- Minas Gerais Research Funding Foundation (FAPEMIG) [APQ-00428-21, APQ-03458-13, APQ-02816-21]
- CAPES/Alexander von Humboldt Foundation [99999.008121/2014-01]
- National Council for Scientific and Technological Development (CNPq) [406048/2018-5, 442731/2020-5, 142097/2019-5, 304158/2019-4]
- CNPq
- INOVA FIOCRUZ Program - Oswaldo Cruz Foundation [VPPCB-007-FIO-18-2-94]
Pamidronate (PAM) shows potential as a therapeutic option for the treatment of human visceral leishmaniasis. It exhibits anti-Leishmania activity in vitro and also modulates the immune response.
Visceral leishmaniasis (VL) is an infectious disease caused by Leishmania infantum (L. infantum). Currently, there are no vaccines and/or prophylactic therapies against VL, and the recentpharmacological approaches come from the drug repositioning strategy. Here, we evaluated the anticancer drug pamidronate (PAM) to identify a new therapeutic option for the treatment of human VL. We assessed its in vitro antileishmanial activity against the promastigote and amastigote forms of L. infantum by evaluating cell cytotoxicity. The antileishmanial and immunomodulatory activities were assessed using human peripheral blood leukocytes ex vivo. PAM induced the formation of vacuoles in the cytoplasm of the promastigotes and alterations in the morphology of the kinetoplast and mitochondria in vitro, which indicates anti-promastigote activity. PAM also reduced the number of infected macrophages and intracellular amastigotes in a concentration-dependent manner, with cell viability above 70%. In ex vivo, PAM reduced the internalized forms of L. infantum in the classical monocyte subpopulation. Furthermore, it enhanced IL-12 and decreased IL-10 and TGF-beta by monocytes and neutrophils. Increased IFN-beta and TNF levels for CD8(-) and CD8(+) T lymphocytes and B lymphocytes, respectively, were observed after the treatment with PAM, as well as a reduction in IL-10 by the lymphocyte subpopulations evaluated. Taken together, our results suggest that PAM may be eligible as a potential therapeutic alternative for drug repurposing to treat human visceral leishmaniasis.
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