Hexadecylphosphocholine induces interferon-γ secretion and expression of GM-CSF mRNA in human mononuclear cells

Platelet-Activating Factor Receptor Contributes to Antileishmanial Function of Miltefosine

“…So, a new orally bioavailable antileishmanial drug was a pressing need, when miltefosine [hexadecylphosphocholine (HPC)], an alkyl-phosphocholine originally developed as an anticancer drug (3), was proved to be an effective antileishmanial agent in clinics (4). Miltefosine is reported to trigger apoptosis-like effects (5), lipid-dependent cell signaling in cancer cells (6), and impaired phospholipid synthesis in the parasite (7), as well as acting as an immunomodulator, promoting macrophage activation (8)(9)(10)(11). Together with our previous report on the host cell signaling-dependent antileishmanial activity of miltefosine (12), these observations imply that miltefosine may work through a cell surface receptor.…”

“…The incorporation of miltefosine into the lipid membrane may alter ligand-bound receptor diffusion and signaling intermediate recruitments to the receptor, causing interference with cellular signaling in cancer cells (7,30). Although these observations supported the direct action of the drug on the parasite, some reports suggest that miltefosine's immunomodulatory functions (9)(10)(11)(12) contribute to the elimination of intracellular amastigotes, although the underlying mechanism for macrophage activation by miltefosine remains unknown. The studies reported in this article indicate that a significant component of the antileishmanial function of miltefosine is executed through PAF receptor.…”

Activities of Hexadecylphosphocholine (Miltefosine), AmBisome, and Sodium Stibogluconate (Pentostam) against Leishmania donovani in Immunodeficient scid Mice

“…The immunomodulatory effects of HPC have been described previously, including its activity as a costimulatory signal for T-cell and macrophage activation in vitro (12,25,31), an enhancer of IFN-␥ production and granulocyte-macrophage colony-stimulating factor expression from peripheral mononuclear human cells in combination with interleukin-2 (13,31), and an inducer of nitric oxide when used in a liposomal HPC preparation on the human histiocyte cell line U937 (12) or peritoneal macrophages after they are triggered with lipopolysaccharide (33). The stimulatory effect of HPC on the hematopoietic system has also been reported; an increased number of white blood cells and platelets were observed after oral treatment of humans with HPC (23).…”

“…The molecular mechanism of action of HPC against cancer cells has been linked to apoptosis as well as different lipid-dependent cell signaling pathways (2), but its mode of action against Leishmania parasites remains unclear. It has also been suggested that HPC has immunomodulatory properties (12,13,31); however, some studies have shown that HPC retains its antitumor properties in immunodeficient mice, suggesting that activity is not dependent on a T-cell-mediated immune response, although increases in macrophage, T-cell, and B-cell numbers were observed (25). Recently, the antileishmanial activity of HPC was shown to be retained in mouse models deficient in T-cell, endogenous gamma interferon (IFN-␥), and macrophage killing (reactive nitrogen and oxygen radicals) mechanisms (18).…”

Interaction of Alkylphospholipid Formulations with Breast Cancer Cells in the Context of Anticancer Drug Development

“…Early interest focussed on immune stimulating activity of alkylphospholipids. It could be demonstrated that Miltefosine and other lipids of this class are able to activate T-cells and macrophages to express and release chemokines like GM-CSF , IFgamma (Hochhuth et al, 1992) and/or nitric oxide (NO) . T h i s e f f e c t c o u l d b e i m p r o v e d i f t h e alkylphospholipids were used in liposomal form.…”