Interleukin‐18 mediated inflammatory brain injury after intracerebral hemorrhage in male mice

Abstract

Interleukin-18 (IL-18), a pro-inflammatory cytokine, is thought to be associated with inflammation in many neurological diseases such as ischemic stroke and poststroke depression, but the role of IL-18 in inflammatory injury after intracerebral hemorrhage (ICH) remains unclear. In this study, we established the ICH model in male mice and found that IL-18 expression including protein and mRNA levels was significantly increased in brain tissues after ICH. Meanwhile, exogenous IL-18 exacerbated cerebral hematoma and neurological deficits following ICH. In the IL-18 knockout group, the size of hematoma and neurological functions after ICH was decreased compared with the wild-type group, suggesting the critical role of IL-18 on the modulation of brain injury after ICH. Importantly, exogenous IL-18 increased microglial activation in brain tissues after ICH. Furthermore, IL-18 knockout resulted in the reduction of activated microglia after ICH. These results indicated that IL-18 may regulate the inflammatory response after ICH through the activation of microglia. Thus, IL-18 is expected to be a promising therapeutic target for secondary brain injury after ICH.

Interleukin-18 cytokine in immunity, inflammation, and autoimmunity: Biological role in induction, regulation, and treatment

“…IL-18 have been shown to be a diagnostic marker and predictor of inflammatory conditions like myocardial ischemia ( 106 ), acute respiratory distress syndrome ( 107 , 108 ), chronic obstructive pulmonary disease ( 109 ), post infectious bronchiolitis obliterans ( 110 ) and sepsis-induced multi organ injury ( 111 ). IL-18 has also received increase attention in the pathophysiology of neuro-vascular diseases such as in intracerebral hemorrhage ( 112 ), Japanese encephalitis ( 113 ), ocular Behcet disease ( 114 ), abdominal aortic aneurysm ( 115 ), amyotrophic lateral sclerosis ( 116 ), glioma ( 117 ) and most interestingly in cognitive impairment ( 118 ) and agitation in severe mental disease ( 119 ).…”

Correlation of Plasmatic Profiles of Inflammatory Cytokines/Chemokines and GFAP with Brain Damage Detected at MRI in Neonates with Hypoxic Ischemic Encephalopathy (HIE) Treated with Therapeutic Hypothermia: A Preliminary Study

“…Therefore, IL-18 seems to play an important role in the development of white matter injury. In neonates treated with TH, IL-18 decreases during the first 24 hours and serum levels seem to be significantly lower in treated than in untreated neonates (25,26). Moreover, IL-18 serum levels seem to correlate with the severity of outcomes (27).…”

“…Although it may be a potential therapeutic target for some inflammation-mediated diseases, the role of IL-18 in intracerebral inflammatory damage still remains unclear. Recent studies in animal models have shown that IL-18 can regulate the inflammatory response following intracerebral hemorrhage (25). Therefore, IL-18 seems to play an important role in the development of white matter injury.…”

Autophagy regulates inflammation in intracerebral hemorrhage: Enemy or friend?

“…Neuroinflammation is a crucial factor in ICH-induced SBI and may develop shortly after ICH and peak a few days later ( Li et al, 2021c ). Inflammation caused by various proinflammatory factors, such as IL-1β, IL-18, and TNF-α, leads to the destruction of the BBB, exacerbated brain edema, and neuronal death ( Tschoe et al, 2020 ; Li H. et al, 2022 ). There are many reactive inflammatory processes after ICH, including microglia activation, inflammatory cytokine release, and leukocyte infiltration ( Figure 3B ; Ye et al, 2021 ).…”