Cytokines ‐ killers in the brain?

Rothwell, Nancy J.

doi:10.1111/j.1469-7793.1999.003af.x

Cited by 225 publications

(121 citation statements)

References 126 publications

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“…TNF-α and IL-1 are increased in cerebral ischemia-In normal brain, expression of most cytokines, including TNF-α and IL-1, is very low (85). TNF-α and IL-1, major pro-inflammatory cytokines, are rapidly up-regulated in brain after cerebral ischemia (84,(87)(88)(89).…”

Section: Tnf-α Il-1 and Il-6 In The Cnsmentioning

confidence: 99%

“…IL-1 signaling is mediated by IL-1 receptor type I, while receptor type II is believed to be a non-signaling or "decoy" receptor (85). IL-1ß is the primary form expressed in the brain and up-regulated in response to stroke (85). Since both forms of IL-1 interact with the same receptor, they are believed to mediate much of the same signaling; however their functions may not completely overlap (77).…”

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confidence: 99%

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confidence: 99%

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Integration of cytokine biology and lipid metabolism in stroke

Adibhatla

Dempsy²,

Hatcher³

2008

Front Biosci

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Cytokines regulate the innate and adaptive immune responses and are pleiotropic, redundant and multifunctional. Expression of most cytokines, including TNF-α and IL-1α/ß, is very low in normal brain. Metabolism of lipids is of particular interest due to their high concentration in the brain. Inflammatory response after stroke suggests that cytokines (TNF-α, IL-1 α/ß, IL-6), affect the phospholipid metabolism and subsequent production of eicosanoids, ceramide, and ROS that may potentiate brain injury. Phosphatidylcholine and sphingomyelin are source for lipid messengers. Sphingomyelin synthase serves as a bridge between metabolism of glycerolipids and sphingolipids. TNF-α and IL-1 α/ß can induce phospholipases (A 2 , C, and D) and sphingomyelinases, and concomitantly proteolyse phosphatidylcholine and sphingomyelin synthesizing enzymes. Together, these alterations contribute to loss of phosphatidylcholine and sphingomyelin after stroke that can be attenuated by inhibiting TNF-α or IL-1 α/ß signaling. Inflammatory responses are instrumental in the formation and destabilization of atherosclerotic plaques. Secretory PLA 2 IIA is found in human atherosclerotic lesions and is implicated in initiation, progression and maturation of atherosclerosis, a risk factor for stroke. Lipoprotein-PLA 2 , part of apolipoprotein B-100 of LDL, plays a role in vascular inflammation and coronary endothelial dysfunction. Cytokine antagonism attenuated secretory PLA 2 IIA actions, suggesting cytokine-lipid integration studies will lead to new concepts contributing to bench-to-bedside transition for stroke therapy.

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Section: Tnf-α Il-1 and Il-6 In The Cnsmentioning

confidence: 99%

mentioning

confidence: 99%

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Integration of cytokine biology and lipid metabolism in stroke

Adibhatla

Dempsy²,

Hatcher³

2008

Front Biosci

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“…62 Given the large number of brain regions that may be primarily or secondarily influenced by head trauma, it is difficult to identify the specific nuclei or pathways subserving the depression. However, since brain trauma is associated with focal increases of IL-1, 63 as are neurodegenerative disorders, the possibility should be considered that the behavioral effects observed in TBI and Parkinsonian patients are associated with heightened cytokine levels.…”

Section: Symptom and Illness Comorbiditymentioning

confidence: 99%

Dysthymia: a review of pharmacological and behavioral factors

et al. 2000

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Although dysthymia, a chronic, low-grade form of depression, has a morbidity rate as high as that of major depression, and increases the risk for major depressive disorder, limited information is available concerning the etiology of this illness. In the present report we review literature concerning the biological and characterological features of dysthymia, the effectiveness of antidepressant treatments, the influence of stressors in the precipitation and maintenance of the disorder, and both quality of life and psychosocial correlates of the illness. We also provisionally suggest that dysthymia may stem from disturbances of neuroendocrine and neurotransmitter functioning (eg, corticotropin releasing hormone and arginine vasopressin within the hypothalamus, or alternatively monoamine variations within several extrahypothalamic sites), and may also involve cytokine activation. The central disturbances may reflect phenotypic variations of neuroendocrine processes or sensitization of such mechanisms. It is suggested that chronic stressor experiences or stressors encountered early in life lead to the phenotypic neurochemical alterations, which then favor the development of the dysthymic state. Owing to the persistence of the neurochemical disturbances, vulnerability to double depression is increased, and in this instance treatment with antidepressants may attenuate the symptoms of major depression but not those of the basal dysthymic state. Moreover, the residual features of depression following treatment may be indicative of underlying neurochemical disturbances, and may also serve to increase the probability of illness recurrence or relapse. Molecular Psychiatry (2000) 5, 242-261.

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“…The cerebral concentrations of proinflammatory cytokines such as interleukin-1h (IL-1h), interleukin-6 (IL-6) and tumour necrosis factor (TNF-a) are raised after exposure to either hypoxia-ischaemia 19 or infection 20 , and have been implicated in the causal pathway of injury in the term brain 5 . Cell damage occurs as a result of direct cytokine-mediated cytotoxicity combined with activation and recruitment of resident microglia, astrocytes and bloodborne leukocytes 21,22 . Partial initiation of these processes by an episode of infection occurring within 24 hours of delivery could affect the fetal response to subsequent hypoxia -ischaemia in various ways: (1) up-regulation of the innate immune system with early initiation of inflammatory processes by hypoxia leading to glial activation and release of cytotoxic cytokines 18 ; (2) increased nitric oxide production leading to mitochondrial dysfunction and failure of oxidative phosphorylation 23 ; (3) endotoxin-induced hypoglycaemia impairing the metabolic response to hypoxia 24 ; (4) exacerbation of local tissue ischaemia via activation of procoagulant molecules and release of vasoactive substances such as platelet-activating factor and endothelial damage; and (5) increased expression of proapoptotic molecules such as Fas ligand or TNF.…”

Section: Combined Effects Of Hypoxia and Infectionmentioning

confidence: 99%