Role of Interleukin-10 in Acute Brain Injuries

Abstract

Interleukin-10 (IL-10) is an important anti-inflammatory cytokine expressed in response to brain injury, where it facilitates the resolution of inflammatory cascades, which if prolonged causes secondary brain damage. Here, we comprehensively review the current knowledge regarding the role of IL-10 in modulating outcomes following acute brain injury, including traumatic brain injury (TBI) and the various stroke subtypes. The vascular endothelium is closely tied to the pathophysiology of these neurological disorders and research has demonstrated clear vascular endothelial protective properties for IL-10. In vitro and in vivo models of ischemic stroke have convincingly directly and indirectly shown IL-10-mediated neuroprotection; although clinically, the role of IL-10 in predicting risk and outcomes is less clear. Comparatively, conclusive studies investigating the contribution of IL-10 in subarachnoid hemorrhage are lacking. Weak indirect evidence supporting the protective role of IL-10 in preclinical models of intracerebral hemorrhage exists; however, in the limited number of clinical studies, higher IL-10 levels seen post-ictus have been associated with worse outcomes. Similarly, preclinical TBI models have suggested a neuroprotective role for IL-10; although, controversy exists among the several clinical studies. In summary, while IL-10 is consistently elevated following acute brain injury, the effect of IL-10 appears to be pathology dependent, and preclinical and clinical studies often paradoxically yield opposite results. The pronounced and potent effects of IL-10 in the resolution of inflammation and inconsistency in the literature regarding the contribution of IL-10 in the setting of acute brain injury warrant further rigorously controlled and targeted investigation.

Immune changes in peripheral blood and hematoma of patients with intracerebral hemorrhage

“…The findings support our recent research, which showed that IL‐10 contributes to macrophage alternative activation, hematoma resolution, and improved neurologic function in an animal model of ICH . Interestingly, preclinical and clinical studies about the role of IL‐10 in acute brain injury yielded opposite results . Further research is needed to investigate whether the changes in the immune system identified in this study could be used as a target for the treatment of ICH.…”

“…17 Interestingly, preclinical and clinical studies about the role of IL-10 in acute brain injury yielded opposite results. 83 Further research is needed to investigate whether the changes in the immune system identified in this study could be used as a target for the treatment of ICH. Instead of using the neutrophil-to-lymphocyte ratio reported in the previous reports, 84,85 we analyzed changes in the granulocyte-to-lymphocyte ratio (GLR) in this study because neutrophils account for a large proportion of granulocytes.…”

Elevated Systemic IL-10 Levels Indicate Immunodepression Leading to Nosocomial Infections after Aneurysmal Subarachnoid Hemorrhage (SAH) in Patients

“…In SAH, IL-10 levels were significantly elevated after SAH and were associated with general cerebral edema [20], which is a prognostic factor for poor clinical outcome in patients. However, detailed preclinical and clinical studies investigating the association between serum IL-10 levels and post-SAH infections are still lacking [21]. The current study was planned to investigate contribution of systemic IL-10 levels during early and delayed brain injury towards the development of post-SAH infections and clinical outcome.…”

Differential effects of typical and atypical antipsychotics on astroglial cells in vitro

“…TNF‐α, IL‐1β and IL‐6 are the most relevant activating cytokines known to act on the CNS; these molecules mediate information between cells and behave like a network, since they can activate cells to produce other cytokines and inflammatory mediators, and promote immune cell infiltration into the brain parenchyma (Colombo and Farina, 2016; Jensen et al, 2013). IL‐10, in contrast, has the ability to attenuate neuroinflammation by suppressing inflammatory pathways and promoting cellular repair processes (Garcia et al, 2017; Strle et al, 2001).…”