Interleukin-1 and Tumor Necrosis Factor-α Synergistically Mediate Neurotoxicity: Involvement of Nitric Oxide and of N-Methyl-D-aspartate Receptors

Chao, Chun C.; Hu, Shuxian X.; Ehrlich, Laura; Peterson, Phillip K.

doi:10.1006/brbi.1995.1033

Cited by 392 publications

(237 citation statements)

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“…IL-1␤ is reported to enhance the death of human fetal brain cells and rat oligodendrocyte progenitor cells, but only when combined with TNF-␣ or INF-␥ (39,40). In the present study, there was no evidence from TUNEL staining that IL-1␤ and/or acute stress elicit hippocampal cell death either in vitro or in vivo, which is consistent with previous studies (40)(41)(42), although there is one report that severe acute stress increases apoptosis (43).…”

Section: Discussionmentioning

confidence: 99%

IL-1β is an essential mediator of the antineurogenic and anhedonic effects of stress

Koo

Duman

2008

Proc. Natl. Acad. Sci. U.S.A.

775

564

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Stress decreases neurogenesis in the adult hippocampus, and blockade of this effect is required for the actions of antidepressants in behavioral models of depression. However, the mechanisms underlying these effects of stress have not been identified. Here, we demonstrate an essential role for the proinflammatory cytokine IL-1␤. Administration of IL-1␤ or acute stress suppressed hippocampal cell proliferation. Blockade of the IL-1␤ receptor, IL-1RI, by using either an inhibitor or IL-1RI null mice blocks the antineurogenic effect of stress and blocks the anhedonic behavior caused by chronic stress exposure. In vivo and in vitro studies demonstrate that hippocampal neural progenitor cells express IL-1RI and that activation of this receptor decreases cell proliferation via the nuclear factor-B signaling pathway. These findings demonstrate that IL-1␤ is a critical mediator of the antineurogenic and depressive-like behavior caused by acute and chronic stress.cytokine ͉ depression ͉ neurogenesis T he profound consequences of stress exposure, defined as disturbances of physiological homeostasis, include a detrimental impact on certain aspects of brain function (1, 2). In particular, uncontrollable stress is a major contributing factor for neuropsychiatric disorders such as major depression and posttraumatic stress disorders (3, 4). Alterations at the cellular level in the hippocampus have been linked to the pathophysiology of stress-related mood disorders (5-7). Many studies demonstrate that stressful experiences suppress hippocampal neurogenesis, which could contribute to the hippocampal atrophy observed in depressed patients (8-10). In contrast, antidepressant treatment increases hippocampal neurogenesis, blocks the antineurogenic effects of stress (11,12), and reduces or even reverses hippocampal atrophy (9, 11). Recent studies demonstrate that new hippocampal neurons are required for the actions of antidepressants in behavioral models of depression and anxiety (13, 14) with some exceptions (15,16).Despite this progress, the mechanisms underlying the antineurogenic and behavioral actions of stress remain ill defined. One possibility is that excessive proinflammatory cytokines, particularly IL-1␤, contribute to the actions of stress. Animal studies demonstrate that exposure to stress increases IL-1␤ in several brain areas, including the hippocampus (17-20), and central administration of IL-1␤ produces several stress-like effects, including activation of the hypothalamic-pituitary-adrenal (HPA) axis (17, 21), inhibition of hippocampal long-term potentiation (22), down-regulation of hippocampal brain-derived neurotrophic factor (23), and impaired hippocampal-dependent contextual fear conditioning (24). In contrast, blockade of the receptor, IL-1RI that mediates the actions of IL-1␤ (25) inhibits these stress-like effects (23, 24) and blocks the antiproliferative effects of INF-␣ in the hippocampus (26).Based on this evidence, the current study was undertaken to test the hypothesis that the antineurogenic and depressiv...

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Section: Discussionmentioning

confidence: 99%

IL-1β is an essential mediator of the antineurogenic and anhedonic effects of stress

Koo

Duman

2008

Proc. Natl. Acad. Sci. U.S.A.

775

564

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“…8 Another report demonstrated that when added individually, these cytokines did not induce the death of neurons, but when administered together, neurodegeneration was observed. 9 In contradiction to these results, Strijbos and Rothwell 10 demonstrated that low concentrations of IL-1b have neuroprotective effects, whereas high concentrations are neurotoxic over a longer term. Westmoreland et al 11 observed that TNF-a is neurodegenerative while IL-1b is not.…”

Section: Innate Immunity and The Central Nervous Systemmentioning

confidence: 96%

Neuroprotective properties of the innate immune system and bone marrow stem cells in Alzheimer's disease

2006

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The role of innate immunity and microglia in the brain is currently a matter of great debate and controversy. While several studies have provided evidence that they contribute to neurodegeneration in various animal models of brain diseases and traumas, others have shown that their inhibition may in contrast be associated with more damages or less repair. We have recently reported the existence of two different types of microglia, the resident and the newly differentiated microglia that derive from the bone marrow stem cells. Of great interest is the fact that blood-derived microglial cells are associated with amyloid plaques and these cells are able to prevent the formation or eliminate the presence of amyloid deposits in mice that develop the major hallmark of Alzheimer's disease (AD). These newly recruited cells are specifically attracted to the b-amyloid 40/42 isoforms in vivo and they participate in the elimination of these proteins by phagocytosis. This review presents the mechanisms involved in the control of the innate immune response by microglia and the beneficial properties of such a response in brain diseases, such as AD.

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“…The potent neurotoxic effects of IL-1 have been shown to be synergistically enhanced in the presence of TNF, suggesting that these crucial cytokines mediate post-traumatic inflammation and secondary brain damage. 49,50 Glial cells secrete both TNF and IL-1, which in turn, activate these cells in an autocrine manner to induce further cytokine production and astrogliosis.…”

Section: Tumor Necrosis Factor-␣mentioning

confidence: 99%

Involvement of Pro- and Anti-Inflammatory Cytokines and Chemokines in the Pathophysiology of Traumatic Brain Injury

2010

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Summary:Despite dramatic improvements in the management of traumatic brain injury (TBI), to date there is no effective treatment available to patients, and morbidity and mortality remain high. The damage to the brain occurs in two phases, the initial primary phase being the injury itself, which is irreversible and amenable only to preventive measures to minimize the extent of damage, followed by an ongoing secondary phase, which begins at the time of injury and continues in the ensuing days to weeks. This delayed phase leads to a variety of physiological, cellular, and molecular responses aimed at restoring the homeostasis of the damaged tissue, which, if not controlled, will lead to secondary insults. The development of secondary brain injury represents a window of opportunity in which pharmaceutical compounds with neuroprotective properties could be administered. To establish effective treatments for TBI victims, it is imperative that the complex molecular cascades contributing to secondary injury be fully elucidated. One pathway known to be activated in response to TBI is cellular and humoral inflammation. Neuroinflammation within the injured brain has long been considered to intensify the damage sustained following TBI. However, the accumulated findings from years of clinical and experimental research support the notion that the action of inflammation may differ in the acute and delayed phase after TBI, and that maintaining limited inflammation is essential for repair. This review addresses the role of several cytokines and chemokines following focal and diffuse TBI, as well as the controversies around the use of therapeutic anti-inflammatory treatments versus genetic deletion of cytokine expression.

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Interleukin-1 and Tumor Necrosis Factor-α Synergistically Mediate Neurotoxicity: Involvement of Nitric Oxide and of N-Methyl-D-aspartate Receptors

Cited by 392 publications

References 0 publications

IL-1β is an essential mediator of the antineurogenic and anhedonic effects of stress

IL-1β is an essential mediator of the antineurogenic and anhedonic effects of stress

Neuroprotective properties of the innate immune system and bone marrow stem cells in Alzheimer's disease

Involvement of Pro- and Anti-Inflammatory Cytokines and Chemokines in the Pathophysiology of Traumatic Brain Injury

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