title: Modulation of the pro- and anti-inflammatory cytokine balance by amphotericin B.
abstract: Amphotericin B is an antifungal drug associated with side effects such as fever and chills, symptoms which may be mediated by pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNFalpha). We assessed the capacity of amphotericin B to modulate production of these pro-inflammatory cytokines as well as the anti-inflammatory IL-1 receptor antagonist (IL-1ra), induced by LPS, heat-killed Candida albicans or Staphylococcus aureus. The results of the present study show that amphotericin B slightly increased the production of pro-inflammatory cytokines by human mononuclear cells (PBMC), whereas the production of the anti-inflammatory cytokine IL-1ra was significantly inhibited. This results in a shift towards pro-inflammatory cytokine production, as indicated by a decreased IL-1ra/IL-1beta ratio. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) indicated that levels of IL-1beta and TNFalpha mRNA were increased. In conclusion, amphotericin B is able to cause a shift towards pro-inflammatory cytokine production by human PBMC. This may explain the side effects, such as fever and chills, observed after treatment of patients with amphotericin B.
authors.affiliation: Department of Medicine, University Hospital Nijmegen, The Netherlands.
authors.forename: A G
authors.initials: AG
authors.lastname: Vonk
authors.forename: M G
authors.initials: MG
authors.lastname: Netea
authors.forename: N E
authors.initials: NE
authors.lastname: Denecker
authors.forename: I C
authors.initials: IC
authors.lastname: Verschueren
authors.forename: J W
authors.initials: JW
authors.lastname: van der Meer
authors.forename: B J
authors.initials: BJ
authors.lastname: Kullberg
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology* / Q000633:toxicity; D000935:Antifungal Agents / Q000494:pharmacology* / Q000633:toxicity; D002176:Candida albicans; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D007375:Interleukin-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D012333:RNA, Messenger / Q000096:biosynthesis; D013211:Staphylococcus aureus; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000935:Antifungal Agents; D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000666:Amphotericin B