This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Simitsopoulou, M.
Right arrow Articles by Walsh, T. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Simitsopoulou, M.
Right arrow Articles by Walsh, T. J.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, April 2005, p. 1397-1403, Vol. 49, No. 4
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.4.1397-1403.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Differential Expression of Cytokines and Chemokines in Human Monocytes Induced by Lipid Formulations of Amphotericin B

M. Simitsopoulou,1,2 E. Roilides,1,3 J. Dotis,1 M. Dalakiouridou,1 F. Dudkova,1,{dagger} E. Andreadou,2 and T. J. Walsh3*

Laboratory of Infectious Diseases, 3rd Department of Pediatrics, School of Medicine, Aristotle University of Thessaloniki,1 Laboratory of Medical Biotechnology, Department of Medical Laboratories, Technological Educational Institute, Thessaloniki, Greece,2 Immunocompromised Host Section, National Cancer Institute, Bethesda, Maryland3

Received 8 August 2004/ Returned for modification 11 October 2004/ Accepted 24 December 2004

The immunomodulatory effects of liposomal amphotericin B (LAMB), amphotericin B lipid complex (ABLC), and amphotericin B colloidal dispersion (ABCD) on mRNA and protein profiles of five cytokines and chemokines expressed by human monocyte-enriched mononuclear leukocytes (MNCs) were comprehensively evaluated by semiquantitative reverse transcription-PCR and enzyme-linked immunosorbent assays; they were compared to those of deoxycholate amphotericin B (DAMB). mRNAs of interleukin-1ß (IL-1ß), IL-1 receptor antagonist (IL-1ra), tumor necrosis factor alpha (TNF-{alpha}), monocyte chemotactic protein 1 (MCP-1), and macrophage inflammatory protein 1ß (MIP-1ß) were assessed after treatment of MNCs with each drug for 0.5, 2, 6, and 22 h. The cytokine protein profiles were obtained after incubation of MNCs with the drugs for 2 h (TNF-{alpha}) or 6 h (all the others). In the mRNA studies, DAMB resulted in an early increase of inflammatory cytokines or chemokines IL-1ß, TNF-{alpha}, MCP-1, and MIP-1ß (2 to 6 h) and in a late increase of anti-inflammatory IL-1ra (22 h). ABCD showed a general similar trend of inflammatory gene up-regulation. LAMB and ABLC decreased or did not affect IL-1ß and TNF-{alpha}, whereas ABLC additionally decreased MIP-1ß. In protein measurement studies, DAMB and ABCD up-regulated production of IL-1ß (P < 0.05), decreased the IL-1ra/IL-1ß ratio, and up-regulated the production of MCP-1 and MIP-1ß. In comparison, LAMB and ABLC down-regulated or did not affect the production of these cytokines/chemokines compared to untreated MNCs; furthermore, ABLC tended to increase the IL-1ra/IL-1ß ratio. These studies demonstrate that amphotericin B formulations differentially affect gene expression and release of an array of proinflammatory and anti-inflammatory cytokines that potentially may explain the differences in infusion-related reactions and dose-dependent nephrotoxicity as well as modulation of the host immune response to invasive fungal infections.

* Corresponding author. Mailing address: Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bldg. 10, Rm 13N240, Bethesda, MD 20892. Phone: (301) 402-0023. Fax: (301) 402-0575. E-mail: walsht{at}mail.nih.gov.

{dagger} Present address: Department of Medical and Biological Sciences, Pharmaceutical Faculty, Heyrovskeho, Hradec Kralove, Czech Republic.

Antimicrobial Agents and Chemotherapy, April 2005, p. 1397-1403, Vol. 49, No. 4
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.4.1397-1403.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Dotis, J., Simitsopoulou, M., Dalakiouridou, M., Konstantinou, T., Panteliadis, C., Walsh, T. J., Roilides, E. (2008). Amphotericin B formulations variably enhance antifungal activity of human neutrophils and monocytes against Fusarium solani: comparison with Aspergillus fumigatus. J Antimicrob Chemother 61: 810-817 [Abstract] [Full Text]  
  • Dotis, J., Simitsopoulou, M., Dalakiouridou, M., Konstantinou, T., Taparkou, A., Kanakoudi-Tsakalidou, F., Walsh, T. J., Roilides, E. (2006). Effects of Lipid Formulations of Amphotericin B on Activity of Human Monocytes against Aspergillus fumigatus. Antimicrob. Agents Chemother. 50: 868-873 [Abstract] [Full Text]  
  • Pai, M. P., Norenberg, J. P., Telepak, R. A., Sidney, D. S., Yang, S. (2005). Assessment of Effective Renal Plasma Flow, Enzymuria, and Cytokine Release in Healthy Volunteers Receiving a Single Dose of Amphotericin B Desoxycholate. Antimicrob. Agents Chemother. 49: 3784-3788 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»