Bergeron Y, Ouellet N, Deslauriers A M, Simard M, Olivier M, Bergeron M G
Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval and Département de Microbiologie, Faculté de Médecine, Université Laval, Sainte-Foy, Québec, Canada G1V 4G2.
Antimicrob Agents Chemother. 1998 Oct;42(10):2527-33. doi: 10.1128/AAC.42.10.2527.
It has recently become apparent that overwhelming inflammatory reactions contribute to the high mortality rate associated with pneumococcal infection in immunocompetent hosts. Cefodizime (CEF) is an antibiotic that seems to be endowed with immunomodulating properties. To investigate the influence of CEF on the pulmonary inflammatory response induced by Streptococcus pneumoniae, we infected mice with repeated intranasal inoculations of 10(7) CFU of heat-killed fluorescein isothiocyanate-labeled bacteria, which are insensitive to the killing properties of the drug. CEF downregulated but did not abolish the strong polymorphonuclear leukocyte (PMN) recruitment induced by S. pneumoniae. PMN recruitment was not primarily mediated by leukotriene B4 in this model. The drug did not interfere with intrinsic mechanisms of phagocytosis by PMNs and alveolar macrophages. CEF totally abrogated the pneumococcus-induced tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) secretion in bronchoalveolar lavage fluid. The drug also prevented IL-6 release in lung homogenates and partly inhibited TNF-alpha, but it did not interfere with IL-1alpha secretion in the lungs of infected mice. The fractional and selective downregulation of inflammatory cells and cytokines by CEF suggests cell-specific and intracellular specific mechanisms of interaction of the drug. The immunomodulatory properties of CEF may help restrain excessive inflammatory reactions, thus contributing to the reported good clinical efficacy of the drug against lower respiratory tract infections.
最近已明显看出，压倒性的炎症反应导致免疫功能正常宿主中与肺炎球菌感染相关的高死亡率。头孢地嗪（CEF）是一种似乎具有免疫调节特性的抗生素。为了研究CEF对肺炎链球菌诱导的肺部炎症反应的影响，我们用10⁷CFU热灭活的异硫氰酸荧光素标记细菌经鼻反复接种感染小鼠，这些细菌对该药物的杀伤特性不敏感。CEF下调但并未消除肺炎链球菌诱导的强烈多形核白细胞（PMN）募集。在该模型中，PMN募集并非主要由白三烯B4介导。该药物并未干扰PMN和肺泡巨噬细胞的内在吞噬机制。CEF完全消除了支气管肺泡灌洗液中肺炎球菌诱导的肿瘤坏死因子α（TNF-α）和白细胞介素-6（IL-6）分泌。该药物还可防止肺匀浆中IL-6的释放，并部分抑制TNF-α，但它并不干扰感染小鼠肺中IL-1α的分泌。CEF对炎症细胞和细胞因子的部分和选择性下调提示了该药物相互作用的细胞特异性和细胞内特异性机制。CEF的免疫调节特性可能有助于抑制过度的炎症反应，从而有助于该药物对下呼吸道感染所报道的良好临床疗效。
