Absence of endogenous interleukin‐10 enhances secondary inflammatory process after spinal cord compression injury in mice

Abstract

Interleukin‐10 (IL‐10) exerts a wide spectrum of regulatory activities in the immune and inflammatory response. The aim of this study was to investigate the role of endogenous IL‐10 on the modulation of the secondary events in mice subjected to spinal cord injury induced by the application of vascular clips (force of 24 g) to the dura via a four‐level T5–T8 laminectomy. IL‐10 wild‐type mice developed severe spinal cord damage characterized by oedema, tissue damage and apoptosis (measured by Annexin‐V, terminal deoxynucleotidyltransferase‐mediated UTP end labeling staining, Bax, Bcl‐2, and Fas‐L expression). Immunohistochemistry demonstrated a marked increase of localization of TNF‐α, IL‐1β and S100β, while western blot analysis shown an increased immunoreactivity of inducible nitric oxide synthase in the spinal cord tissues. The absence of IL‐10 in IL‐10 KO mice resulted in a significant augmentation of all the above described parameters. We have also demonstrated that the genetic absence of IL‐10 worsened the recovery of limb function when compared with IL‐10 wild‐type mice group (evaluated by motor recovery score). Taken together, our results clearly demonstrate that the presence of IL‐10 reduces the development of inflammation and tissue injury events associated with spinal cord trauma.

Acid Fibroblast Growth Factor and Peripheral Nerve Grafts Regulate Th2 Cytokine Expression, Macrophage Activation, Polyamine Synthesis, and Neurotrophin Expression in Transected Rat Spinal Cords

“…Th2 cells promote facial motoneuron survival after facial nerve axotomy, but a reduced survival rate has been reported in IL-4 knock-out mice (Deboy et al, 2006). More severe secondary inflammatory responses have been reported in IL-10 knock-out mice, resulting in worse functional recovery after spinal cord compression (Genovese et al, 2009). Moreover, treatment of contused rat spinal cords with IL-10 reportedly improves motor function recovery (Bethea et al, 1999).…”

Applications of the Keap1–Nrf2 system for gene and cell therapy

“…In addition to in vitro studies, increased NF-κB binding activity in the spinal cord has been reported in vivo after compression SCI [103] and increased levels of TNF are observed in the spinal cords of Nrf2-deficient mice [97,103] . Due to its relatively specific cytotoxicity towards oligodendrocytes, TNF may be one of the main factors responsible for the damage of these cells and pronounced demyelination after SCI [104][105][106] .…”

Chinese Angelica Polysaccharide (CAP) Alleviates LPS-Induced Inflammation and Apoptosis by Down-Regulating COX-1 in PC12 Cells

“…The secondary injury is mediated by multiple injury processes, including inflammation, free radical-induced cell death, and glutamate excitotoxicity [7]. Inflammatory response contributes a lot in the regulation of SCI pathogenesis, and seems to play a pivotal role in nerve injury and regenerative response [8]. In addition, inflammatory response may contribute to the apoptosis of neurons and oligodendrocytes as well as to the loss of neuronal function [9].…”