JAC Advance Access published online on August 13, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg367
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Department of Medical Microbiology and Infectious Diseases,
Erasmus Medical Center Rotterdam,
Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands
Received 20 March 2003
; revised 12 June 2003
; accepted 12 June 2003
Objective: The kinetics of various
parameters of fungal load and cytokines were investigated, in order
to acquire insight into the pathogenesis of invasive pulmonary aspergillosis
(IPA) during antifungal treatment with amphotericin B. Methods: Neutropenic rats with left-sided IPA
received either treatment with amphotericin B or remained untreated.
At 0, 4, 8, 16, 24, 48, 72 and 120 h after fungal inoculation, the
rats were dissected. The size of the macroscopic pulmonary lesions,
the number of cfu and amounts of chitin were determined in the infected left
lung. Galactomannan concentrations were measured both in the left
lung and serum. The cytokines tumour necrosis factor (TNF)- Results: Amphotericin B treatment of IPA resulted
in changed aspect of pulmonary lesions and significantly reduced
levels of left lung chitin (72 and 120 h), left lung galactomannan
(72 and 120 h) and serum galactomannan (120 h), but not left lung
cfu, compared with untreated infected rats. In addition, amphotericin
B treatment resulted in a significant decrease in levels of left
lung IL-6 (at 72 and 120 h), MIP-2 (at 120 h) and MCP-1 (at 120
h). No local or systemic increases in TNF- Conclusion: It is concluded that treatment with
amphotericin B results in decreased fungal load in the infected
lung. This reduction in fungal load probably results in a decreased
local inflammatory response, as measured by decreased levels of
IL-6, MIP-2 and MCP-1 in the infected lung.
Keywords: chemokines, interleukins, chitin, galactomannan, Aspergillus
Effect of amphotericin B treatment on kinetics
of cytokines and parameters of fungal load in neutropenic rats with
invasive pulmonary aspergillosis
,
interleukin (IL)-1
, IL-6, interferon
(IFN)-
, IL-4, IL-10, and the chemokines macrophage
inflammatory protein (MIP)-2 and monocyte chemoattractant protein
(MCP)-1 were determined quantitatively by ELISA in the infected
left lung, uninfected right lung and serum.,
IL-1 or IFN- were
observed during infection.
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