Department of Medical Microbiology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre, P. Debyelaan 25, 6229 HZ, Maastricht, The Netherlands.
Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands.
Inflammopharmacology. 2017 Dec;25(6):643-651. doi: 10.1007/s10787-017-0359-7. Epub 2017 May 20.
Patients with more severe chronic obstructive pulmonary disease frequently experience exacerbations and it is estimated that up to 50% of these exacerbations are associated with bacterial infections. The mainstay treatment for these infection-related exacerbations constitutes the administration of glucocorticoids, alone or in combination with antibiotics. A recent line of evidence demonstrates that many hormones including the steroid beclomethasone can also directly affect bacterial growth, virulence, and antibiotic resistance. The effect of these regimens on the release of potentially virulent and toxic membrane vesicles (MVs) is at present unclear. In this study, we determined the effect of several pharmacological agents on MVs release by and bacterial growth of common respiratory pathogens. We found that neither the release of MVs nor the bacterial growth was affected by the glucocorticoids budesonide and fluticasone. The macrolide antibiotic azithromycin only inhibited the growth of Moraxella catarrhalis but no effects were observed on bacterial MV release at a concentration that is achieved locally in the epithelial lining on administration. The macrophage pro-inflammatory response to MVs was significantly reduced after treatment with budesonide and fluticasone but not by azithromycin treatment. Our findings suggest that these glucocorticoids may have a positive effect on infection-related inflammation although the bacterial growth and MV release remained unaffected.
患有更严重慢性阻塞性肺疾病的患者经常会经历恶化，据估计，这些恶化中有多达 50%与细菌感染有关。这些与感染相关的恶化的主要治疗方法是单独或联合使用抗生素给予糖皮质激素。最近的一系列证据表明，许多激素，包括类固醇倍氯米松，也可以直接影响细菌的生长、毒力和抗生素耐药性。这些方案对潜在毒力和毒性膜囊泡 (MVs) 的释放的影响目前尚不清楚。在这项研究中，我们确定了几种药理制剂对常见呼吸道病原体的 MV 释放和细菌生长的影响。我们发现，糖皮质激素布地奈德和氟替卡松既不影响 MV 的释放，也不影响细菌的生长。大环内酯类抗生素阿奇霉素仅抑制卡他莫拉菌的生长，但在给药时上皮衬里局部达到的浓度下，对细菌 MV 释放没有观察到任何作用。用布地奈德和氟替卡松处理后，巨噬细胞对 MV 的促炎反应明显降低，但阿奇霉素处理则没有。我们的研究结果表明，这些糖皮质激素可能对与感染相关的炎症有积极影响，尽管细菌生长和 MV 释放不受影响。
