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Antimicrobial Agents and Chemotherapy, February 2004, p. 396-403, Vol. 48, No. 2
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.2.396-403.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Antibody Array-Generated Profiles of Cytokine Release from THP-1 Leukemic Monocytes Exposed to Different Amphotericin B Formulations

Lloyd W. Turtinen,^1* David N. Prall,¹ Lindsay A. Bremer,¹ Rachel E. Nauss,² and Scott C. Hartsel²

Department of Biology,¹ Department of Chemistry, University of Wisconsin—Eau Claire, Eau Claire, Wisconsin 54702²

Received 26 June 2003/ Returned for modification 29 August 2003/ Accepted 9 November 2003

Cytokine antibody arrays were used to establish the profiles of cytokine release from THP-1 monocytes exposed to different amphotericin B (AMB) drug delivery systems. Fungizone (FZ) and Amphotec (ABCD) caused the release of significantly more inflammatory molecules and the release of inflammatory molecules at higher levels than either AmBisome (L-AMB) or Abelcet (ABLC) after 6 h of treatment. Specifically, tumor necrosis factor alpha (TNF-), interleukin-8 (IL-8), GRO-(ß), monocyte chemoattractant protein-1 (MCP-1), RANTES, IL-10, and IL-6 were detected and semiquantified with a chemiluminscence imaging system. TNF-, IL-8, and MCP-1 were the most predominant; however, little if any TNF- was present in ABLC- or L-AMB-treated cultures. The TNF- and IL-8 levels determined by quantitative enzyme-linked immunosorbent assay correlated with the relative cytokine levels measured by using the antibody arrays. Although the viabilities of THP-l monocytes in all AMB-treated cultures were similar by trypan blue exclusion, the amount of lactic dehydrogenase released was significantly larger in FZ- and ABCD-treated cultures than in L-AMB- and ABLC-treated cultures, indicating more membrane perturbations with those formulations. Membrane cation channel formation was also measured in model cholesterol-containing large unilamellar vesicles to directly assess the ion channel formation ability of the system. Only FZ and ABCD induced significant ion currents at concentrations less than 1.5 x 10^-5 M. These results may help provide rationales for the immediate cytokine-mediated side effects observed with FZ and ABCD and the reduced side effects observed with L-AMB and ABLC.

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* Corresponding author. Mailing address: Department of Biology, University of Wisconsin—Eau Claire, 105 Garfield Ave., Eau Claire, WI 54702. Phone: (715) 836-3506. Fax: (715) 836-5089. E-mail: Turtinen{at}uwec.edu.

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Antimicrobial Agents and Chemotherapy, February 2004, p. 396-403, Vol. 48, No. 2
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.2.396-403.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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