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

Repurposing Miltefosine for the Treatment of Immune-Mediated Disease?

“…In a similar experiment with macrophages isolated from C57BL/6 mice, there was no increase in NO release, but miltefosine did increase their phagocytic capacity. Not only did sensitized macrophages phagocytize more Saccharomyces cerevisiae after miltefosine treatment, but miltefosine also increased the number of macrophages that participated in the process (Ponte et al, 2012).…”

Effectiveness of miltefosine-pentoxifylline compared to miltefosine in the treatment of cutaneous leishmaniasis in C57Bl/6 mice

“…The use of drugs with immunomodulatory effects to treat CL is primarily motivated by the need for alternatives to the standard treatment (pentavalent antimony), and has shown promising results in relapse cases 8,15 . The use of combined pentoxifyllinemiltefosine treatments could help reduced drug resistance to miltefosine, as well as possibly increase the effi cacy of treatment…”

“…The drug exerts its cytotoxic effect by interfering with the metabolism of membrane phospholipids, altering the composition, permeability, stability, and fluidity of the cell membrane, subsequently inducing apoptos is 3,6 . Miltefosine's mechanism of action also indirectly induces immunomodulatory antileishmanial mechanisms by increasing production of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin 12 (IL-12), thereby increasing phagocytosis and inducing an immune response biased towards a Th1 profi le 7,8 .…”

“…Similarly, pentoxifylline (a methylxanthine) has been investigated in the treatment of CL, based on its inhibition of nuclear factor kappa beta (NF-kβ), TNF-α, and intercellular adhesion molecule 1 (ICAM-1) 8,9 , as well as its nephroprotective effect when combined with antimonials 10 . These immunomodulatory effects may help to regulating patients' exacerbated and inefficient intracellular immune response to parasites, and subsequently reduce tissue infl ammation.…”

Rhynchophylline prevents cardiac dysfunction and improves survival in lipopolysaccharide-challenged mice via suppressing macrophage I-κBα phosphorylation

“…Peritoneal macrophages were obtained according to the previously described methods [16]. In brief, macrophages were collected by washing the peritoneal cavity with cold phosphate-buffered saline (PBS, 10 mL) and cultured in RPMI-1640 (supplemented with 20 mM Hepes, 2 mM glutamine, 100 U/mL penicillin, 100 μg/mL streptomycin and 10% FBS, pH 7.2) at 37°C for 12 h in an atmosphere of 5% CO 2 .…”