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JAC Advance Access published online on January 6, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg070
© 2003 by The British Society for Antimicrobial Chemotherapy
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© 2003 The British Society for Antimicrobial Chemotherapy

Brief report

Heat-induced superaggregation of amphotericin B attenuates its ability to induce cytokine and chemokine production in the human monocytic cell line THP-1

P. David Rogers 1*, Katherine S. Barker 2, Vanessa Herring 2, Melissa Jacob 3

1 Departments of Clinical Pharmacy and Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 26 South Dunlap Street, Memphis, TN 38163
2 Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, 26 South Dunlap Street, Memphis, TN 38163
3 National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS 38677, USA

* Corresponding author. E-mail: drogers{at}utmem.edu.

Received 27 June 2002 ; revised 1 November 2002

Abstract

The cytokine and chemokine response elicited by heat-treated amphotericin B (HT-AmB) was compared with that of untreated amphotericin B (AmB-DOC) in the human monocyte cell line THP-1. AmB-DOC produced dose-dependent increases in interleukin (IL)-1{beta}, IL-1{alpha}, tumour necrosis factor-{alpha}, macrophage inflammatory protein (MIP)-1{alpha} and MIP-1{beta} at 2 h. HT-AmB induced cytokine and chemokine production at a lower level than those observed with corresponding concentrations of AmB-DOC, while retaining antifungal activity. These results indicate that heat treatment of amphotericin B may prove to be a cost-effective approach to improving the therapeutic index of this antifungal agent.

Keywords: amphotericin B, monocyte, cytokine, chemokine
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