Mesenchymal stem cells significantly improved treatment effects of Linezolid on severe pneumonia in a rabbit model.

Dexiao Kong,Yibo Dai,Lihong Zhang,Ai Li,Chengyun Zheng,Juan Xiao,Ruodi Cui,Xiaoyan Li,Fang Wang,Yang Jiang,Xiaoli Liu,Mingming He,Wei Wang,Xia Liu,Jianting Hu,Juandong Wang,Xiaomei Li,Yuan Zhang

doi:10.1042/bsr20182455

Dexiao Kong, Yibo Dai + Show 16 more

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https://doi.org/10.1042/bsr20182455

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Abstract

The present study aimed to investigate whether co-administration of mesenchymal stromal cells (MSC) and linezolid (LZD) into a rabbit model of methicillin-resistant Staphylococcus aureus (MRSA)-infected pneumonia would bring a synergistic therapeutic effect. Human umbilical cord-derived MSCs (hUMSCs) were isolated and characterized. A rabbit model of pneumonia was constructed by delivering 1 × 1010 CFU MRSA via a bronchoscope into the basal segment of lower lobe of right lung. Through analyzing vital sign, pulmonary auscultation, SpO2, chest imaging, bronchoscopic manifestations, pathology, neutrophil percentage, and inflammatory factors, we verified that a rabbit model of MRSA-induced pneumonia was successfully constructed. Individual treatment with LZD (50 mg/kg for two times/day) resulted in improvement of body weight, chest imaging, bronchoscopic manifestations, histological parameters, and IL-10 concentration in plasma (P<0.01), decreasing pulmonary auscultation, and reduction of IL-8, IL-6, CRP, and TNF-α concentrations in plasma (P<0.01) compared with the pneumonia model group at 48 and 168 h. Compared with LZD group, co-administration of hUMSCs (1 × 106/kg for two times at 6 and 72 h after MRSA instillation) and LZD further increased the body weight (P<0.05). The changes we observed from chest imaging, bronchoscopic manifestations and pathology revealed that co-administration of hUMSCs and LZD reduced lung inflammation more significantly than that of LZD group. The plasma levels of IL-8, IL-6, CRP, and TNF-α in combined group decreased dramatically compared with the LZD group (P<0.05). In conclusion, hUMSCs administration significantly improved therapeutic effects of LZD on pneumonia resulted from MRSA infection in a rabbit model.

Highlights

Methicillin-resistant Staphylococcus aureus (MRSA), isolated frequently from both community and hospital settings, is one of the major pathogenic microorganisms for nosocomial infections that lead to considerable morbidity and mortality [1,2]
In the early stage of our study, we investigated the degree of pneumonia caused by different concentrations of MRSA
We found that endotracheal directed instillation of 1 ×108 and 1 × 109 colony forming units (CFU) MRSA in outbred rabbits through bronchoscope resulted in no mortality

Summary

Introduction

Methicillin-resistant Staphylococcus aureus (MRSA), isolated frequently from both community and hospital settings, is one of the major pathogenic microorganisms for nosocomial infections that lead to considerable morbidity and mortality [1,2]. Linezolid (LZD) was recommended as a standard choice for the treatment of MRSA nosocomial pneumonia [3], the ratio of morbidity and mortality associated. With MRSA infections is still high [4]. The best treatment for this potentially life-threatening infection has not been definitely defined. More and more researches demonstrated that the severe pneumonia involves in the imbalance between pathogen and immune system of the host [5]. The interest in immunotherapy alternatives and its potential role in treating MRSA infections is arising

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