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转化生长因子-β中和对铜绿假单胞菌烧伤创面感染小鼠模型生存及细菌清除的影响

Effect of transforming growth factor-beta neutralization on survival and bacterial clearance in a murine model of Pseudomonas aeruginosa burn wound infection.

作者信息

Huang Zhiyu, Pereira Clifford, Toliver-Kinsky Tracy, Murphey Erle D, Varma Tushar K, Lin Cheng Y, Herndon David N, Sherwood Edward R

机构信息

Shriners Hospitals for Children, Galveston, Texas, USA.

出版信息

J Burn Care Res. 2006 Sep-Oct;27(5):682-7. doi: 10.1097/01.BCR.0000238083.95170.2A.

DOI:10.1097/01.BCR.0000238083.95170.2A
PMID:16998401
Abstract

Transforming growth factor-beta (TGF-beta), a cytokine with anti-inflammatory properties, may contribute to postburn immunosuppression. This study was designed to determine whether neutralizing TGF-beta in burned mice could improve resistance to infection. C57BL/6J mice received a 35% TBSA flame burn under isoflurane anesthesia. Four days after injury, mice were treated with TGF-beta antibody or nonspecific IgG. On day 5 after burn injury, mice were inoculated with Pseudomonas aeruginosa at the burn wound site or received intraperitoneal injection with P. aeruginosa. Mice treated with anti-TGF-beta exhibited significantly improved survival compared with mice treated with nonspecific IgG after challenge with P. aeruginosa at the burn wound site or after intraperitoneal injection of P. aeruginosa. In mice with burn wound infections, bacterial counts in burn wounds, blood, and lung were decreased in mice treated with anti-TGF-beta compared with mice treated with control IgG. Bacterial counts in lung and blood after intraperitoneal challenge with P. aeruginosa also were significantly lower in burned mice treated with anti-TGF-beta compared with those treated with nonspecific IgG. Our data suggest that neutralization of TGF-beta at 4 days after burn injury in mice improves local and systemic clearance of P. aeruginosa and enhances survival after P. aeruginosa challenge.

摘要

转化生长因子-β(TGF-β)是一种具有抗炎特性的细胞因子,可能导致烧伤后免疫抑制。本研究旨在确定中和烧伤小鼠体内的TGF-β是否能提高抗感染能力。C57BL/6J小鼠在异氟烷麻醉下接受35%体表面积的火焰烧伤。受伤4天后,小鼠接受TGF-β抗体或非特异性IgG治疗。烧伤后第5天,在烧伤创面接种铜绿假单胞菌或腹腔注射铜绿假单胞菌。在烧伤创面接种铜绿假单胞菌或腹腔注射铜绿假单胞菌后,与接受非特异性IgG治疗的小鼠相比,接受抗TGF-β治疗的小鼠存活率显著提高。在有烧伤创面感染的小鼠中,与接受对照IgG治疗的小鼠相比,接受抗TGF-β治疗的小鼠烧伤创面、血液和肺中的细菌计数减少。与接受非特异性IgG治疗的小鼠相比,接受抗TGF-β治疗的烧伤小鼠在腹腔注射铜绿假单胞菌后的肺和血液中的细菌计数也显著降低。我们的数据表明,在小鼠烧伤后4天中和TGF-β可改善铜绿假单胞菌的局部和全身清除,并提高铜绿假单胞菌攻击后的存活率。

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引用本文的文献

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The Toll-like receptor 4 agonist monophosphoryl lipid a augments innate host resistance to systemic bacterial infection.Toll 样受体 4 激动剂单磷酰脂质 A 增强固有宿主对全身细菌感染的抵抗力。
Infect Immun. 2011 Sep;79(9):3576-87. doi: 10.1128/IAI.00022-11. Epub 2011 Jun 6.
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Topical nanoemulsion therapy reduces bacterial wound infection and inflammation after burn injury.局部纳米乳剂疗法可减少烧伤感染后的细菌感染和炎症。
Surgery. 2010 Sep;148(3):499-509. doi: 10.1016/j.surg.2010.01.001. Epub 2010 Mar 2.