Liposomal Amphotericin B and Amphotericin B–Deoxycholate Show Different Immunoregulatory Effects on Human Peripheral Blood Mononuclear Cells

Abstract

Conventional preparations of amphotericin B (AmB) at established therapeutic doses are known to increase nonspecific immune responses. It remains to be established whether higher doses of the less toxic liposomal preparation of AmB maintains a beneficial effect on the immune response to fungal infections. Examination of the effect of treatment of human peripheral blood mononuclear cells from healthy subjects with various doses of both liposomal AmB (L-AmB) and deoxycholate AmB (d-AmB) on proliferation, cell viability, and percentage of apoptosis demonstrated that, although both L-AmB and d-AmB at low doses significantly increased nonspecific proliferative responses, L-AmB, but not d-AmB, treatment maintained this beneficial effect at higher doses. High doses of d-AmB, but not L-AmB, resulted in significantly decreased cell viability and increased apoptosis. This study provides further evidence in healthy human subjects for choosing L-AmB over conventional preparations in the clinical treatment of fungal infections requiring systemic high-dose treatment with AmB.

Real-Time Reverse Transcription-PCR Quantification of Cytokine mRNA Expression in Golden Syrian Hamster Infected withLeishmania infantumand Treated with a New Amphotericin B Formulation

“…This dual effect would create a clinical cure in most animals (unpublished data). The reason for this dual effect could be a dose-dependent immunomodulatory effect of the new formulation similar to that observed by Reyes et al (27) with liposomal AMB on human peripheral blood mononuclear cells. Liposomal AMB maintained increased nonspecific proliferative responses against fungal infections at doses that are toxic for the conventional nonliposomal formulation (deoxycholate AMB).…”

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

“…The immunomodulatory effects of amphotericin B have been reported previously (6,24), but they do not appear to play a role in the antileishmanial activity of this drug (20). In contrast to the similar activities of HPC and AmBisome in scid and BALB/c mice, sodium stibogluconate was significantly less active in scid mice.…”

Multidrug-Resistant Trichosporon asahii Infection of Nongranulocytopenic Patients in Three Intensive Care Units

“…This emphasizes the importance of the patient's basic immune status in determining the outcomes of such infections. Furthermore, one should bear in mind that AMB might have modulatory effects on the immune system by upregulating the expression of proinflammatory cytokines and activating the mononuclear cells (37,43). Hence, in vitro resistance to antifungal drugs may not be critical in immunocompetent patients, who may overcome the infection when the precipitating cause (e.g., a catheter) is removed, even if only partial inhibition of fungal growth is achieved through the use of antifungal drugs.…”