Effects of amphotericin B and caspofungin on histamine expression.
OBJECTIVE
To determine the effects of amphotericin B deoxycholate and caspofungin on the release of histamine from human peripheral blood cells, mononuclear cells, and mast cells.


METHODS
In vitro cell culture experiments.


METHODS
University medical center.


METHODS
Cultured human mononuclear (THP-1) and mast (HMC-1) cells from five healthy volunteers.


RESULTS
The cultured cells were incubated with increasing concentrations of amphotericin B deoxycholate, diphenhydramine, amphotericin B deoxycholate plus diphenhydramine, caspofungin, caspofungin plus diphenhydramine, and the calcium ionophore A23187 for up to 24 hours. Histamine concentrations and histamine N-methyltransferase activity were determined at various time points throughout exposure. Cell viability was assessed by exclusion of erythrocin B. The A23187 increased histamine concentrations from baseline in peripheral blood and HMC-1 cells. No change in histamine concentrations was observed in response to amphotericin B deoxycholate, whereas caspofungin induced a significant increase in histamine release in peripheral blood cells and HMC-1 cells. No change in histamine concentrations was observed in THP-1 cells in response to any pharmacologic agent tested. Similarly, histamine N-methyltransferase activity in peripheral blood was not affected by amphotericin B deoxycholate, but was significantly decreased by caspofungin.


CONCLUSIONS
Amphotericin B deoxycholate does not affect histamine concentrations or histamine N-methyltransferase activity in whole blood or HMC-1 cells, suggesting that the amphotericin B-induced infusion-related reaction is not a histamine-mediated event. Conversely, caspofungin increased histamine concentrations in whole blood and HMC-1 cells and inhibited histamine N-methyltransferase activity. These data suggest that infusion-related reactions associated with caspofungin may be mediated by histamine release secondary to caspofungin.
Cleary
John D
JD
Department of Clinical Pharmacy, University of Mississippi School of Pharmacy, Jackson 39216, USA.
Schwartz
Michael
M
Rogers
P David
PD
de Mestral
Jacqueline
J
Chapman
Stanley W
SW
D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D000077336:Caspofungin; D002478:Cells, Cultured; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004338:Drug Combinations; D054714:Echinocandins; D006632:Histamine / Q000097:blood; D017442:Histamine Agonists / Q000494:pharmacology*; D006637:Histamine N-Methyltransferase / Q000037:antagonists & inhibitors / Q000097:blood; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D055666:Lipopeptides; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D010456:Peptides, Cyclic
D000935:Antifungal Agents; D004338:Drug Combinations; D054714:Echinocandins; D017442:Histamine Agonists; D055666:Lipopeptides; D010455:Peptides; D010456:Peptides, Cyclic; D003840:Deoxycholic Acid; D000666:Amphotericin B; D006632:Histamine; C059765:amphotericin B, deoxycholate drug combination; D006637:Histamine N-Methyltransferase; D000077336:Caspofungin