Anti-inflammatory effects of antibacterials on human bronchial epithelial cells

被引:28
作者
Zimmermann, Gregor S. [1 ]
Neurohr, Claus [1 ]
Villena-Hermoza, Heidrun [1 ]
Hatz, Rudolf [2 ]
Behr, Juergen [1 ]
机构
[1] Univ Munich, Klinikum Grosshadern, Dept Internal Med 1, Div Pulm Dis, D-8000 Munich, Germany
[2] Univ Munich, Klinikum Grosshadern, Div Thorac Surg, D-8000 Munich, Germany
来源
RESPIRATORY RESEARCH | 2009年 / 10卷
关键词
OBSTRUCTIVE PULMONARY-DISEASE; NF-KAPPA-B; BRONCHIOLITIS OBLITERANS SYNDROME; AIR-FLOW OBSTRUCTION; PSEUDOMONAS-AERUGINOSA; CYSTIC-FIBROSIS; RESPIRATORY PATHOGENS; MACROLIDE ANTIBIOTICS; KINASE ACTIVATION; CEFUROXIME AXETIL;
D O I
10.1186/1465-9921-10-89
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Background: Human Bronchial epithelial cells (hu-BEC) have been claimed to play a significant role in the pathogenesis of chronic inflammatory airway diseases like COPD. In this context IL-8 and GM-CSF have been shown to be key cytokines. Some antibiotics which are routinely used to treat lower respiratory tract infections have been shown to exert additional immunomodulatory or anti-inflammatory effects. We investigated whether these effects can also be detected in hu-BEC. Methods: Hu-BEC obtained from patients undergoing lung resections were transferred to air-liquid-interface (ALI) culture. These cultures were incubated with cefuroxime (CXM, 10-62.5 mg/l), azithromycin (AZM, 0.1-1.5 mg/l), levofloxacin (LVX, 1-8 mg/l) and moxifloxacin (MXF, 1-16 mg/l). The spontaneous and TNF-alpha (10 ng/ml) induced expression and release of IL-8 and GM-CSF were measured using PCR and ELISA in the absence or presence of these antibiotics. Results: The spontaneous IL-8 and GM-CSF release was significantly reduced with MXF (8 mg/l) by 37 +/- 20% and 45 +/- 31%, respectively (both p < 0.01). IL-8 release in TNF-alpha stimulated hu-BEC decreased by 16 +/- 8% (p < 0.05) with AZM (1.5 mg/l). With MXF a concentration dependent decrease of IL-8 release was noted up to 39 +/- 7% (p < 0.05). GM-CSF release from TNF-alpha stimulated hu-BEC was maximally decreased by 35 +/- 24% (p < 0.01) with MXF (4 mg/l). Conclusion: Using ALI cultures of hu-BEC we observed differential effects of antibiotics on spontaneous and TNF-a induced cytokine release. Our data suggest that MXF and AZM, beyond bactericidal effects, may attenuate the inflammatory process mediated by hu-BEC.
引用
收藏
页数:8
相关论文
共 38 条
[2]   Human chemokines: An update [J].
Baggiolini, M ;
Dewald, B ;
Moser, B .
ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 :675-705
[3]   BRONCHOALVEOLAR DISTRIBUTION OF CEFUROXIME AXETIL AND INVITRO EFFICACY OF OBSERVED CONCENTRATIONS AGAINST RESPIRATORY PATHOGENS [J].
BALDWIN, DR ;
ANDREWS, JM ;
WISE, R ;
HONEYBOURNE, D .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1992, 30 (03) :377-385
[4]  
Bals Robert, 2004, J Cyst Fibros, V3 Suppl 2, P49, DOI 10.1016/j.jcf.2004.05.010
[5]   Chronic obstructive pulmonary disease: molecular and cellular mechanisms [J].
Barnes, PJ ;
Shapiro, SD ;
Pauwels, RA .
EUROPEAN RESPIRATORY JOURNAL, 2003, 22 (04) :672-688
[6]   Moxifloxacin but not ciprofloxacin or azithromycin selectively inhibits IL-8, IL-6, ERK1/2, JNK, and NF-κB activation in a cystic fibrosis epithelial cell line [J].
Blau, Hannah ;
Klein, Keren ;
Shalit, Itamar ;
Halperin, Drora ;
Fabian, Ina .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2007, 292 (01) :L343-L352
[7]   Steady-state intrapulmonary concentrations of moxifloxacin, levofloxacin, and azithromycin in older adults [J].
Capitano, B ;
Mattoes, HM ;
Shore, E ;
O'Brien, A ;
Braman, S ;
Sutherland, C ;
Nicolau, DP .
CHEST, 2004, 125 (03) :965-973
[8]   Airflow obstruction after myeloablative allogeneic hematopoietic stem cell transplantation [J].
Chien, JW ;
Martin, PJ ;
Gooley, TA ;
Flowers, ME ;
Heckbert, SR ;
Nichols, WG ;
Clark, JG .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2003, 168 (02) :208-214
[9]   ASSESSMENT OF CEFAZOLIN AND CEFUROXIME TISSUE PENETRATION BY USING A CONTINUOUS INTRAVENOUS-INFUSION [J].
CONNORS, JE ;
DIPIRO, JT ;
HAYTER, RG ;
HOOKER, KD ;
STANFIELD, JA ;
YOUNG, TR .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1990, 34 (06) :1128-1131
[10]   Immunomodulatory effects of quinolones [J].
Dalhoff, A ;
Shalit, L .
LANCET INFECTIOUS DISEASES, 2003, 3 (06) :359-371