Release of TNF-α and IL-1β from porcine brain endothelium corresponds to the pyrogenic potential of three marketed formulations of amphotericin

T. R. McGuire, W. J. Trickler, L. Smith, E. B. Hoie, D. W. Miller

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Background: Formulations of amphotericin include a deoxycholate suspension (d-Amph), an amphotericin-B lipid complex (Ablc), and a liposomal product (L-Amph). Fever is most frequent with d-Amph, intermediate with Ablc, and lowest with L-Amph. Objective: To determine if the release of tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1) from brain endothelium corresponds to the incidence of amphotericin fever. Results: Release of TNF-α and IL-1β after L-Amph treatment was similar to negative controls while after d-Amph treatment release was similar to lipopolysaccharide. Ablc treatment produced intermediate pyrogen release. NF-κB expression, a transcriptional regulator for TNF-α and IL-1β genes, corresponded to this secretion pattern. TNF-α release was elevated 2 hours (p = 0.0021) after treatment while significant elevations in IL-1β required 6 hours (p = 0.0009). Conclusion: Results from this in vitro study suggest that amphotericin fever may be directly mediated by brain endothelium. These experiments also suggest that amphotericin fever is initially mediated by TNF-α.

Original languageEnglish (US)
Pages (from-to)375-379
Number of pages5
JournalInflammation Research
Volume54
Issue number9
DOIs
StatePublished - Sep 2005

Keywords

  • Amphotericin fever
  • Brain endothelium
  • TNF-α

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

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