Becker Martin J, de Marie Siem, Fens Marcel H A M, Verbrugh Henri A, Bakker-Woudenberg Irma A J M
Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center Rotterdam, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
J Antimicrob Chemother. 2003 Sep;52(3):428-34. doi: 10.1093/jac/dkg367. Epub 2003 Aug 13.
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.
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)-alpha, interleukin (IL)-1beta, IL-6, interferon (IFN)-gamma, 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.
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-alpha, IL-1beta or IFN-gamma were observed during infection.
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.
研究真菌负荷和细胞因子各项参数的动力学变化，以便深入了解两性霉素B抗真菌治疗期间侵袭性肺曲霉病（IPA）的发病机制。
左侧患IPA的中性粒细胞减少大鼠接受两性霉素B治疗或不治疗。在真菌接种后0、4、8、16、24、48、72和120小时，解剖大鼠。测定感染的左肺中宏观肺部病变的大小、菌落形成单位（cfu）数量和几丁质含量。检测左肺和血清中的半乳甘露聚糖浓度。通过酶联免疫吸附测定法（ELISA）定量测定感染的左肺、未感染的右肺和血清中的细胞因子肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β、IL-6、干扰素（IFN）-γ、IL-4、IL-10以及趋化因子巨噬细胞炎性蛋白（MIP）-2和单核细胞趋化蛋白（MCP）-1。
与未治疗的感染大鼠相比，两性霉素B治疗IPA导致肺部病变外观改变，左肺几丁质水平（72和120小时）、左肺半乳甘露聚糖水平（72和120小时）和血清半乳甘露聚糖水平（120小时）显著降低，但左肺cfu无变化。此外，两性霉素B治疗导致左肺IL-6水平（72和120小时）、MIP-2水平（120小时）和MCP-1水平（120小时）显著降低。感染期间未观察到TNF-α、IL-1β或IFN-γ的局部或全身升高。
得出结论，两性霉素B治疗可降低感染肺中的真菌负荷。这种真菌负荷的降低可能导致局部炎症反应减弱，如通过感染肺中IL-6、MIP-2和MCP-1水平降低所测得的那样。
