Keratinocyte growth factor-2 inhibits bacterial infection with Pseudomonas aeruginosa pneumonia in a mouse model.

Abstract

To determine protective effects of concurrent administration of Keratinocyte growth factor-2 (KGF-2) with Pseudomonas aeruginosa (P. aeruginosa) inoculation on the induced pneumonia. KGF-2 (5 mg/kg) was concurrently administered into the left lobe of 55 mice with P. aeruginosa PAO1 (5 × 10(6) CFU, half-lethal dose); 55 mice in the control group were concurrently administered PBS with the PAO1. We detected and analyzed: body temperature; amount of P. aeruginosa in homogenates; count of total number of nucleated cells and of mononuclear macrophages; protein concentration in bronchoalveolar lavage fluid (BALF); lung wet-to-dry weight ratio; cytokines in BALF and blood; and lung morphology. To study survival rate, concurrent administration of KGF-2 (experimental group) versus PBS (control) with a lethal dose of PAO1 (1 × 10(7) CFU was performed, and survivorship was documented for 7 days post-inoculation. The bacterial CFU in lung homogenates was significantly decreased in the KGF-2 group compared to the control group. There were significantly more mononuclear macrophages in the BALF from the KGF-2 group than from the control group (p < 0.05). KGF-2 increased the surfactant protein and GM-CSF mRNA in lung at 6 h and 72 h after inoculation. Significant reduction of lung injury scores, protein concentrations, lung wet-to-dry weight ratio, and IL-6 and TNF-α levels was noted in the KGF-2 treated rats at 72 h after inoculation (p < 0.05). The 7-day survival rate of the KGF-2 group was significantly higher than that of the control group (p < 0.05). Concurrent administration of KGF-2 facilitates the clearance of P. aeruginosa from the lungs, attenuates P. aeruginosa-induced lung injury, and extends the 7-day survival rate in mice model with P. aeruginosa pneumonia.

• Authors: Nana Feng, Qin Wang, Jian Zhou, Jing Li, Xiaoxing Wen, Shujing Chen, Zhenhua Zhu, Chunxue Bai, Yuanlin Song, Huayin Li
• Journal: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy (J Infect Chemother) Vol. 22 Issue 1 Pg. 44-52 (Jan 2016) ISSN: 1437-7780 [Electronic] Netherlands
• PMID: 26617350 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Fibroblast Growth Factor 10
• Interleukin-6
• Tumor Necrosis Factor-alpha
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Animals
• Anti-Bacterial Agents (administration & dosage, therapeutic use)
• Bronchoalveolar Lavage Fluid (microbiology)
• Fibroblast Growth Factor 10 (administration & dosage, therapeutic use)
• Granulocyte-Macrophage Colony-Stimulating Factor (metabolism)
• Interleukin-6 (metabolism)
• Lung (microbiology, pathology)
• Mice
• Pseudomonas Infections (drug therapy, metabolism)
• Pseudomonas aeruginosa
• Rats
• Tumor Necrosis Factor-alpha (metabolism)