alexa Granulocyte-Macrophage Colony-Stimulating Factor Partially Restores Toll-Like Receptor-Mediated Functional Responses of Monocytes in Septic Shock | OMICS International | Abstract
ISSN: 2376-0311

JBR Journal of Clinical Diagnosis and Research
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Research Article

Granulocyte-Macrophage Colony-Stimulating Factor Partially Restores Toll-Like Receptor-Mediated Functional Responses of Monocytes in Septic Shock

Bauer SB1*, Pietropaoli AP1, Georas SN1,2,3, and Williams MA1,2,4*

1Department of Medicine, Division of Pulmonary and Critical Care Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA

2Department of Environmental Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA

3Department of Microbiology and Immunology, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA

4Lung Biology and Disease Program, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA

Corresponding Author:
Stephen M. Bauer
Department of Biology
Belmont Abbey College
100 Belmont Mt. Holly Road, 28012, Belmont, NC 28012, USA
Tel: 212-410-2094
E-mail: [email protected]

Received Date: September 20, 2016; Accepted Date: October 19, 2016; Published Date: October 24, 2016

Citation: Bauer SB, Pietropaoli AP, Georas SN, Williams MA (2016) Granulocyte-Macrophage Colony-Stimulating Factor Partially Restores Toll- Like Receptor-Mediated Functional Responses of Monocytes in Septic Shock. J Clin Diagn Res 4:131. doi: 10.4172/2376-0311.1000131

Copyright: © 2016 Bauer SB, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Septic shock remains clinically challenging to manage. The dysregulated immune response seen in septic shock contributes to this complexity. However, biological response modifiers including the cytokine recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) might be important in managing both septicemia and septic shock. We hypothesized that ex vivo stimulation with rHuGM-CSF could restore functional and phenotypic responses of monocytes. The functional responses of complex whole blood and highly-enriched monocyte cultures were assessed from a panel of n=30 human study subjects (n=23, septic shock and n=7 healthy controls). Cultures were initially primed with rHuGM-CSF then stimulated with relevant toll-like receptor (TLR) ligands for short (4 h) or extended (48 h) time-periods. TLR-specific ligands included lipopolysaccharide (LPS, a surrogate of gram-negative bacterial infection) and double-stranded RNA (dsRNA, a surrogate of a viral infection). Endpoints included measurement of cell surface receptors by flow cytometry and cytokine secretion by multiplex bead-array technology. We found depressed expression of immune cell-surface markers on septic shock monocytes as compared to normal controls. However, a trend of partially restored cell surface expression of functionally important phenotypic markers on septic shock monocytes was associated with restored, or even augmented, cytokine secretion following rHuGM-CSF-priming and secondary stimulation with LPS or dsRNA. A dysregulated pattern of cell activation typically characterizes septic shock and may contribute to inadvertent immune suppression of monocytes. We have showed that rHuGM-CSF priming restored several important aspects of monocyte responsiveness to exogenous bacterial and viral stimuli. This approach could offer therapeutic utility that nonetheless requires empirical proof of concept.

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