Heat-induced superaggregation of amphotericin B attenuates its ability to induce cytokine and chemokine production in the human monocytic cell line THP-1.
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)-1beta, IL-1alpha, tumour necrosis factor-alpha, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta 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.
Rogers
P David
PD
Departments of Clinical Pharmacy and Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 26 South Dunlap Street, Memphis, TN 38163, USA. drogers@utmem.edu
Barker
Katherine S
KS
Herring
Vanessa
V
Jacob
Melissa
M
D000666:Amphotericin B / Q000494:pharmacology* / Q000633:toxicity; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000633:toxicity; D002449:Cell Aggregation / Q000187:drug effects; D002460:Cell Line; D018925:Chemokines / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis*; D005658:Fungi / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D007202:Indicators and Reagents; D008826:Microbial Sensitivity Tests; D009000:Monocytes / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D018925:Chemokines; D016207:Cytokines; D007202:Indicators and Reagents; D000666:Amphotericin B