Interleukin‐10 modulates neuronal threshold of vulnerability to ischaemic damage

Abstract

Interleukin-10 (IL-10) is a powerful suppressor of cellular immune responses, with a postulated role in brain inflammation. First, we have evaluated the role of this cytokine in ischaemic brain damage using IL-10 knockout (IL-10-/-) mice. The middle cerebral artery (MCA) was occluded in either IL-10-/- or wild-type animals of corresponding strain (C57Bl/6) and age. Infarct volume was assessed 24 h later in serial brain sections. Brain infarct produced by MCA occlusion was 30% larger in the IL-10-/- than in wild-type mice (21. 8 +/- 1.2 vs. 16.9 +/- 1.0 mm3, respectively; P < 0.01; Student's t-test). To further characterize these findings, studies were extended to in vitro models. Primary neuronal cortical cultures derived from IL-10-/- animals were more susceptible to both excitotoxicity and combined oxygen-glucose deprivation compared with cell cultures from wild-type mice. Moreover, when added to the culture medium, recombinant murine IL-10 (0.1-100 ng/mL) exerted a concentration-dependent prevention of neuronal damage induced by excitotoxicity in both cortical and cerebellar granule cell cultures taken from either strain. The accordance of in vivo and in vitro data allows us to suggest a potential neuroprotective role of IL-10 against cerebral ischaemia when administered exogenously or made available from endogenous sources.

Interleukin-10 endogenously expressed in microglia prevents lipopolysaccharide-induced neurodegeneration in the rat cerebral cortex in vivo

“…Although the mechanisms underlying the ability of the brain to control inflammation are poorly understood, it has been reported that microglia in culture expressed IL-10 following exposure to LPS (Williams et al, 1996;Seo et al, 2004), and that IL-10 could exert immunosuppressive properties by downregulating the expression of pro-inflammatory cytokines such as TNF-α and IL-12 by microglia (Aloisi et al, 1997(Aloisi et al, , 1999b. Further, several studies have demonstrated neuroprotective effects of IL-10 against glutamate-mediated cerebellar granule cell death, hypoxic-ischemic neuronal cell death, and traumatic brain injury (Knoblach and Faden, 1998;Dietrich et al, 1999;Grilli et al, 2000;Bachis et al, 2001). These data strengthen the notion that the anti-inflammatory phox , p47 phox , and Rac 1 subunit from the cytosol to the plasma membrane; this translocation was sustained by IL-10NA.…”

PreImplantation factor promotes neuroprotection by targeting microRNA let-7

“…IL-10, an anti-inflammatory cytokine, has a well-established role in neuroprotection (42)(43)(44)(45). In addition to acting on glia and endothelium to reduce inflammatory responses following ischemic brain damage, it directly protects cortical neurons by activating the PI3K/AKT pathway via IL-10 receptors on neurons (45).…”

Inflammation-Mediated Damage in Progressing Lacunar Infarctions

“…42 Other experiments have shown that the infusion of a low dose of IL-1 receptor antagonist causes a 71% reduction in the volume of infarction induced by NMDA-receptor activation, 43 whereas the administration of IL-10, which has been related to neuroprotective actions, results in a reduction in glutamate-induced neuronal death. 44 One of the major questions in our study is whether increased inflammatory molecules in blood are the expression of brain ischemia or originate as a result of the acute-phase reaction or systemic causes. Several facts support the idea that plasma levels of IL-6, TNF-␣, and ICAM-1 within the first 24 hours of acute stroke reflect the total release of these molecules in the ischemic brain tissue.…”