Systemic Inflammation and the Breakdown of Intestinal Homeostasis Are Key Events in Chronic Spinal Cord Injury Patients.

Elisa Lopez-Dolado,Carlos Martinez-Alonso,Dimitrios Balomeros,Melchor Alvarez-Mon,David Diaz,Agustín Albillos,Jorge Monserrat,Sergio Haro

doi:10.3390/ijms22020744

Abstract

Our aim was to investigate the subset distribution and function of circulating monocytes, proinflammatory cytokine levels, gut barrier damage, and bacterial translocation in chronic spinal cord injury (SCI) patients. Thus, 56 SCI patients and 28 healthy donors were studied. The levels of circulating CD14+highCD16−, CD14+highCD16+, and CD14+lowCD16+ monocytes, membrane TLR2, TLR4, and TLR9, phagocytic activity, ROS generation, and intracytoplasmic TNF-α, IL-1, IL-6, and IL-10 after lipopolysaccharide (LPS) stimulation were analyzed by polychromatic flow cytometry. Serum TNF-α, IL-1, IL-6 and IL-10 levels were measured by Luminex and LPS-binding protein (LBP), intestinal fatty acid-binding protein (I-FABP) and zonulin by ELISA. SCI patients had normal monocyte counts and subset distribution. CD14+highCD16− and CD14+highCD16+ monocytes exhibited decreased TLR4, normal TLR2 and increased TLR9 expression. CD14+highCD16− monocytes had increased LPS-induced TNF-α but normal IL-1, IL-6, and IL-10 production. Monocytes exhibited defective phagocytosis but normal ROS production. Patients had enhanced serum TNF-α and IL-6 levels, normal IL-1 and IL-10 levels, and increased circulating LBP, I-FABP, and zonulin levels. Chronic SCI patients displayed impaired circulating monocyte function. These patients exhibited a systemic proinflammatory state characterized by enhanced serum TNF-α and IL-6 levels. These patients also had increased bacterial translocation and gut barrier damage.

Highlights

We investigated thethe expression of TLR2, TLR4 and TLR9 in circulating monocytes cytes from both groups of subjects
We found a significant decrease in the percentage of monocytes that expressed TLR4 in group 1 compared to the values observed for healthy controls (HCs)
We have demonstrated that chronic spinal cord injury (SCI) patients without associated inflammatory and infectious diseases show functional impairment of circulating monocytes, with diminished TLR4 expression, increased LPS-induced TNF-α production and defective phagocytosis

Summary

Introduction

Spinal cord injury (SCI) is a cause of severe health problems and disability [1]. The acute stage of the disease is characterized by the induction of a neurological lesion of the spinal cord and the associated clinical manifestations and systemic stress responses determined by the etiopathogenesis of the SCI [2,3,4,5,6,7]. It is well known that acute SCI patients show an intense disturbance of immuneinflammatory responses, which includes hallmarks of inflammation and immunodeficiency [12,13]. At injury sites in the spinal cord, the infiltration of immune cells, including monocytes/macrophages, is involved in determining the extent of the initial tissue damage and causing secondary neural destruction during the first several weeks postinjury [2,14]

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Methods

Conclusion