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

JBR Journal of Clinical Diagnosis and Research
Open Access

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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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Author(s): Bauer SB, Pietropaoli AP, Georas SN and Williams MA


Monocyte, Anergy, Biomarkers, Septic shock, Granulocyte-macrophage colony-stimulating factor, Clinical Echocardiography, Diagnosis of cancer, COPD Diagnosis

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