Interleukin-6 mediates enhanced thrombus development in cerebral arterioles following a brief period of focal brain ischemia

Abstract

Objective The cerebral microvasculature is rendered more vulnerable to thrombus formation following a brief (5.0 min) period of focal ischemia. This study examined the contribution of interleukin-6 (IL-6), a neuroprotective and prothrombotic cytokine produced by the brain, to transient ischemia-induced thrombosis in cerebral arterioles. Approach & results The middle cerebral artery of C57BL/6J mice was occluded for 5 minutes, followed by 24 hrs of reperfusion (MCAo/R). Intravital fluorescence microscopy was used to monitor thrombus development in cerebral arterioles induced by light/dye photoactivation. Thrombosis was quantified as the time of onset of platelet aggregation on the vessel wall and the time for complete blood flow cessation. MCAo/R in wild type (WT) mice yielded an acceleration of thrombus formation that was accompanied by increased IL-6 levels in plasma and in post-ischemic brain tissue. The exaggerated thrombosis response to MCAo/R was blunted in WT mice receiving an IL-6 receptor-blocking antibody and in IL-6 deficient (IL-6−/−) mice. Bone marrow chimeras, produced by transplanting IL-6−/− marrow into WT recipients, did not exhibit protection against MCAo/R-induced thrombosis. Conclusions The increased vulnerability of the cerebral vasculature to thrombus development after MCAo/R is mediated by IL-6, which is likely derived from brain cells rather than circulating blood cells. These findings suggest that anti-IL-6 therapy may reduce the likelihood of cerebral thrombus development after a transient ischemic attack.

Lung injury caused by paraquat poisoning results in increased interleukin‑6 and decreased microRNA‑146a levels

“…IL-6 is an inflammatory factor that has been extensively studied. It induces the production of C-reactive proteins and fibrinogen in inflammation, and promotes thrombosis (17). Increased levels of IL-6 in the body may cause inflammatory diseases, including rheumatoid arthritis and Crohn's disease, due to binding to the IL-6 receptors (18).…”

Ethanol Iris tenuifolia extract reduces brain damage in a mouse model of cerebral ischaemia

“…Under experimental conditions, cerebral ischaemia caused by permanent MCAO also produces a transient increase in IL-6 bioactivity in the ischaemic hemisphere (Loddick, Turnbull, & Rothwell, 1998;Verma et al, 2016;Yamashita et al, 2005). Moreover, increases in plasma IL-6 concentration (or mRNA) have been described (Chapman et al, 2009;Gertz et al, 2012;Offner, Vandenbark, & Hurn, 2009;Tang, Vital, Russell, Seifert, & Granger, 2015;Terao et al, 2008). This observation was explained by IL-6 production being an inflammatory response to acute hypoxic-ischaemic injury (Cojocaru et al, 2009;Dziedzic, Gryz, Turaj, Slowik, & Szczudlik, 2004).…”

“…This observation was explained by IL-6 production being an inflammatory response to acute hypoxic-ischaemic injury (Cojocaru et al, 2009;Dziedzic, Gryz, Turaj, Slowik, & Szczudlik, 2004). It was suggested that circulating cells account for all of the rise in plasma IL-6 concentration (Tang et al, 2015). This IL seems to play a dual role.…”

Research of expression quantity of serum miR-146a and miR-146b in patients with acute cerebral infarction before and after the intervention of rosuvastatin

“…IL-1β and IL-17 have toxic effect on neuron and gliocyte around the infarction focus, and they can lead to the cellular damage and necrocytosis [23,24]. While IL-6 has the effect of endogenous chemotactic factor, which can recruit the inflammatory cells at local focus and mediate the cascade amplification of inflammatory response [25,26]. We can sum up by analyzing the contents of the above inflammatory factors of serum before and after the rosuvastatin treatment that the contents of TNF-α, IL-1β, IL-6 and IL-17 of serum in patients with acute cerebral infarction after treatment were significantly lower than those before the treatment.…”