Proinflammatory cytokines in serum of patients with acute cerebral ischemia: kinetics of secretion and relation to the extent of brain damage and outcome of disease

Tanaka

J Cereb Blood Flow Metab

2008

220

177

Interleukin-6 (IL-6) is pleiotropic cytokine involved in many central nervous system disorders including stroke, and elevated serum IL-6 has been found in acute stroke patients. IL-6 is implicated in the inflammation, which contributes to both injury and repair process after cerebral ischemia. However, IL-6 is one of the neurotrophic cytokines sharing a common receptor subunit, gp130, with other neurotrophic cytokines, such as leukemia inhibitory factor (LIF) and ciliary neurotrophic factor. The expression of IL-6 is most prominently identified in neurons in the peri-ischemic regions, and LIF expression shows a similar pattern. The direct injection of these cytokines into the brain after ischemia can reduce ischemic brain injury. The cytokine receptors are localized on the neuron surface, suggesting that neurons are the cytokine target. The major IL-6 downstream signaling pathway is JAK-STAT, and Stat3 activation occurs mainly in neurons during postischemic reperfusion. Further investigation is necessary to clarify the exact role of Stat3 signaling in neuroprotection. Taken together, the information suggests that IL-6 plays a double role in cerebral ischemia, as an inflammatory mediator during the acute phase and as a neurotrophic mediator between the subacute and prolonged phases.

Section: Serum Interleukin-6 In Stroke Patientsmentioning

confidence: 87%

Ambivalent Aspects of Interleukin-6 in Cerebral Ischemia: Inflammatory versus Neurotrophic Aspects

Tanaka

J Cereb Blood Flow Metab

2008

220

177

“…Typical conditions leading to increased extracellular glutamate concentrations (Bullock et al, 1995;Rothman, 1984;Sandberg et al, 1986;Drejer et al, 1985;Beneviste et al, 1984) are depolarization of neurons, energy depletion due to hypoglycaemia or hypoxia Mattson, 1991, 1992;Cheng et al, 1994;Wieloch, 1985), exposure to nitric oxide (NO) (Bonfoco et al, 1996;Leist et al, 1997a) or defects in the glutamate reuptake systems (Rothstein et al, 1996). In addition, it has recently become clear that concomitant production of cytokines or other mediators can participate in cerebral damage (Chao et al, 1995;Philippon et al, 1994;Fassbender et al, 1994;Mitrovic et al, 1994).…”

Section: Mitochondria and Neuronal Demisementioning

confidence: 99%

Energy supply and the shape of death in neurons and lymphoid cells

1997

Apoptosis and necrosis are considered as conceptually distinct forms of cell death. Nevertheless, there is increasing evidence that classical apoptosis and necrosis represent only the extreme ends of a wide range of possible morphological and biochemical deaths. The two classical types of demise can occur simultaneously in tissues or cell cultures exposed to the same stimulus, and often the intensity of the same initial insult decides the prevalence of either apoptosis or necrosis. This suggests that, while some early events may be common to both types of cell death, a downstream controller may be required to direct cells towards the organised execution of apoptosis. We have recently shown that intracellular energy levels and mitochondrial function are rapidly compromised in necrosis, but not in apoptosis of neuronal cells. Then, we went on to show that pre-emptying human T cells of ATP switches the type of demise caused by two classic apoptotic triggers (staurosporin and CD95 stimulation) from apoptosis to necrosis. Conditions of controlled intracellular ATP depletion, which was obtained by blocking mitochondrial and/or glycolytic ATP generation, were used in combination with repletion of the cytosolic ATP pool with glucose to redirect the death program towards apoptosis or necrosis. At least two distinct steps, the typical nuclear degradation, and the expression of annexin V-recognisable determinants on the cell surface require sufficient ATP generation. This suggests that some upstream regulators of cell death may be common to both types of cell demise, whereas yet unknown downstream processes decide its shape and the implications for the neighbouring tissue.

“…IL-6 is a multifunctional cytokine produced by various types of cells and regulates the immune response, hematopoiesis, the acute phase response and inflammation [3] and is related to mortality and severity of acute diseases in the Emergency Department [4]. Moreover, in numerous previous studies of ischemic stroke it has been found that increased levels of pro-inflammatory cytokines were related to a greater extent of cerebral infarct and poorer clinical outcome [5,6]. The aim of our study was to measure the inflammatory cytokine IL-6 serially in acute ischemic stroke patients and to see their association with stroke severity and outcome.…”

Section: Saroj Choudhary Debashish Chowdhury Tkmishra Sarita Agamentioning

confidence: 99%

Temporal Profile of Serum Levels of Il-6 in Acute Ischemic Stroke and Its Relationship With Stroke Severity and Outcome in Indian Population

Choudhary¹,

Chowdhury²,

Mishra³

et al. 2018

IJIMS