Effects of amphotericin B and caspofungin on histamine expression

John D. Cleary, Michael Schwartz, Phillip Rogers, Jacqueline De Mestral, Stanley W. Chapman

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Study 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. Design. In vitro cell culture experiments. Setting. University medical center. Material. Cultured human mononuclear (THP-1) and mast (HMC-1) cells from five healthy volunteers. Measurements and Main 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. Conclusion. 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.

Original languageEnglish (US)
Pages (from-to)966-973
Number of pages8
JournalPharmacotherapy
Volume23
Issue number8
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

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caspofungin
Amphotericin B
Histamine
Histamine N-Methyltransferase
Diphenhydramine
Histamine Release
Calcimycin
Blood Cells
Calcium Ionophores
Erythromycin
Mast Cells
deoxycholate drug combination amphotericin B
Cultured Cells
Cell Survival
Healthy Volunteers

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)

Cite this

Cleary, J. D., Schwartz, M., Rogers, P., De Mestral, J., & Chapman, S. W. (2003). Effects of amphotericin B and caspofungin on histamine expression. Pharmacotherapy, 23(8), 966-973. https://doi.org/10.1592/phco.23.8.966.32875

Effects of amphotericin B and caspofungin on histamine expression. / Cleary, John D.; Schwartz, Michael; Rogers, Phillip; De Mestral, Jacqueline; Chapman, Stanley W.

In: Pharmacotherapy, Vol. 23, No. 8, 01.08.2003, p. 966-973.

Research output: Contribution to journalArticle

Cleary, JD, Schwartz, M, Rogers, P, De Mestral, J & Chapman, SW 2003, 'Effects of amphotericin B and caspofungin on histamine expression', Pharmacotherapy, vol. 23, no. 8, pp. 966-973. https://doi.org/10.1592/phco.23.8.966.32875
Cleary, John D. ; Schwartz, Michael ; Rogers, Phillip ; De Mestral, Jacqueline ; Chapman, Stanley W. / Effects of amphotericin B and caspofungin on histamine expression. In: Pharmacotherapy. 2003 ; Vol. 23, No. 8. pp. 966-973.
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abstract = "Study 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. Design. In vitro cell culture experiments. Setting. University medical center. Material. Cultured human mononuclear (THP-1) and mast (HMC-1) cells from five healthy volunteers. Measurements and Main 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. Conclusion. 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.",
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