Differential effects of amphotericin B and liposomal amphotericin B on inflammatory cells in vitro.
OBJECTIVE
To understand whether the pseudo-allergic reactions to amphotericin B (AmB) administration are due to AmB or to the solubilizing vehicles, a study was designed to evaluate the effects of AmB, liposomal AmB, (L-AmB), AmB-deoxycholate micellar complex (AmB-DC) and deoxycholate (DC) on the responses of rat serosal mast cells (RSMC) and of human basophils (HB), in vitro.


METHODS
Serosal mast cells were obtained by density gradient centrifugations from male Wistar albino rats. Partially purified HB were obtained from healthy donors. The cells were exposed to AmB, L-AmB, AmB-DC and DC. Histamine release was measured fluorometrically, and the release of lactic dehydrogenase (LDH) was measured spectrophotometrically. HB activation was evaluated cytofluorimetrically by CD63 expression.


RESULTS
AmB and L-AmB did not evoke histamine or LDH release from either RSMC or HB. CD63 expression was not induced in HB challenged with AmB and L-AMB. On the other hand, AmB-DC and DC produced a cytotoxic histamine release from both RSMC and HB, and a sustained increase of CD63 expression on HB.


CONCLUSIONS
Only AmB-DC was able to induce the release of inflammatory mediators from RSMC and HB. Conceivably, the cytotoxic effect is accounted for by the micellar complexes with DC, which has been confirmed as a powerful histamine releaser, and held responsible for the pseudo-allergic reactions after AmB-DC administration. The data lend support to a better safety profile of L-AmB.
Baronti
R
R
Department of Preclinical and Clinical Pharmacology, Mario Aiazzi Mancini, University of Florence, Italy.
Masini
E
E
Bacciottini
L
L
Mannaioni
P F
PF
D000666:Amphotericin B / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D001491:Basophils; D002499:Centrifugation, Density Gradient; D003840:Deoxycholic Acid / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007249:Inflammation / Q000473:pathology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008081:Liposomes; D008407:Mast Cells; D010641:Phenotype; D051381:Rats
D008081:Liposomes; D003840:Deoxycholic Acid; D007073:Immunoglobulin E; D000666:Amphotericin B; D007770:L-Lactate Dehydrogenase