Action site of circulating interleukin-1 on the rabbit brain

Hashimoto, Masaaki; Ishikawa, Yuji; Yokota, Sadaki; Goto, F; Bando, Takehiko; Sakakibara, Yoichi; Iriki, Masami

doi:10.1016/0006-8993(91)90510-3

Cited by 84 publications

(27 citation statements)

References 19 publications

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“…Therefore, molecules up to 500 kDa, including IL-1, can be found in these organs after iv injection. 56,57 Moreover, cells in CVOs express I-B and IL-1␤ mRNA after injection of low doses of LPS which do not induce these mRNAs at the BBB. 58 This indicates that the source of a peripheral IL-1 and TNF-␣ signal propagation is predominantly at the level of CVOs.…”

Section: Systemically Elicited Cytokine Signalingmentioning

confidence: 99%

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Cytokine signals propagate through the brain

et al. 2000

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Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF␣) are proinflammatory cytokines that are constitutively expressed in healthy, adult brain where they mediate normal neural functions such as sleep. They are neuromodulators expressed by and acting on neurons and glia. IL-1 and TNF␣ expression is upregulated in several important diseases/disorders. Upregulation of IL-1 and/or TNF␣ expression, elicited centrally or systemically, propagates through brain parenchyma following specific spatio-temporal patterns. We propose that cytokine signals propagate along neuronal projections and extracellular diffusion pathways by molecular cascades that need to be further elucidated. This elucidation is a prerequisite for better understanding of reciprocal interactions between nervous, endocrine and immune systems. Molecular Psychiatry (2000) 5, 604-615.

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Section: Systemically Elicited Cytokine Signalingmentioning

confidence: 99%

“…56,57 This makes CVO an ideal pathway for the propagation of systemic signals into the brain parenchyma. Systemic LPS elicits fever at the level of the OVLT.…”

Section: Propagation By Diffusion Through the Csfmentioning

confidence: 99%

Cytokine signals propagate through the brain

et al. 2000

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“…79 Additionally, exposure of cultured ECs to ammonia stimulated the release of cytokines and free radicals, all of which are known to enhance inflammatory responses in other conditions. Further, receptors for CKs, including IL-1b and TNF-a, have been identified in brain ECs in experimental models of sepsis, 81 and that activation of these receptors further stimulated the synthesis and release of additional CKs leading to an exacerbation of the brain edema in acute HE. 82 To examine whether ammonia, CKs and LPS stimulate ECs to release inflammatory mediators that may contribute to the astrocyte swelling and brain edema in AHE, primary cultures of rat brain endothelial cells were treated with ammonia, CKs and LPS and the conditioned medium derived from these treatments were added to cultured astrocytes and cell volume was determined.…”

Section: Cerebral Endothelial Cells (Ecs)mentioning

confidence: 99%

Neuroinflammation in Hepatic Encephalopathy: Mechanistic Aspects

Jayakumar

Rao

Norenberg

2015

Journal of Clinical and Experimental Hepatology

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Hepatic encephalopathy (HE) is a major neurological complication of severe liver disease that presents in acute and chronic forms. While elevated brain ammonia level is known to be a major etiological factor in this disorder, recent studies have shown a significant role of neuroinflammation in the pathogenesis of both acute and chronic HE. This review summarizes the involvement of ammonia in the activation of microglia, as well as the means by which ammonia triggers inflammatory responses in these cells. Additionally, the role of ammonia in stimulating inflammatory events in brain endothelial cells (ECs), likely through the activation of the toll-like receptor-4 and the associated production of cytokines, as well as the stimulation of various inflammatory factors in ECs and in astrocytes, are discussed. This review also summarizes the inflammatory mechanisms by which activation of ECs and microglia impact on astrocytes leading to their dysfunction, ultimately contributing to astrocyte swelling/ brain edema in acute HE. The role of microglial activation and its contribution to the progression of neurobehavioral abnormalities in chronic HE are also briefly presented. We posit that a better understanding of the inflammatory events associated with acute and chronic HE will uncover novel therapeutic targets useful in the treatment of patients afflicted with HE. ( J CLIN EXP HEPATOL 2015;5:S21-S28) H epatic encephalopathy (HE) is the major neurological complication of severe liver disease. It presents in two forms, chronic HE and acute HE. Chronic HE (portal-systemic encephalopathy) usually occurs in patients with alcoholic liver cirrhosis and is characterized by impaired neurological function, including changes in personality, altered mood, diminished intellectual capacity, and abnormal muscle tone and tremor. 1 Acute HE (AHE, acute liver failure, ALF; fulminant hepatic failure) generally occurs following massive liver necrosis due to viral hepatitis (hepatitis B and C), hepatic neoplasms, vascular causes, or exposure to acetaminophen and other hepatotoxins. AHE is associated with the abrupt onset of delirium, seizures, and coma.The principal pathological change in chronic HE is characterized by Alzheimer type II astrocytosis, 2,3 which is characterized by astrocytes possessing enlarged, pale nuclei, often occurring in pairs, with the nuclei frequently displaying prominent nucleoli. Cerebral edema and associated increase in intracranial pressure leading to brain herniation are the characteristic features of AHE which occurs in upto 80% of patients with AHE 4-6 and represents the most frequent cause of death in these patients (70% mortality). 4,7 While the basis for the edema in AHE is poorly understood, astroglial swelling (cytotoxic edema) dominates the pathology in experimental animals, [8][9][10][11] as well as in humans. 12 Of interest, no significant or consistent morphologic changes have been identified in neurons or other neural cells. Such findings prompted the suggestion that HE fundamentally represents a pr...

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“…Several possible mechanisms (Breder, Dinarello & Saper, 1988;Sirko, Bishai & Coceani, 1989;Katsuura, Arimura, Koves & Gottschall, 1990;Hashimoto et al 1991) by which blood-borne cytokines might exert their effects on the central nervous system (CNS) have been identified. One such mechanism is direct transport into the CNS by a saturable transport system located at the blood-brain barrier (BBB).…”

mentioning

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Blood‐borne interleukin‐1 alpha is transported across the endothelial blood‐spinal cord barrier of mice.

Banks

Kastin

Ehrensing

1994

The Journal of Physiology

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1. Previous work has shown that one mechanism by which blood-borne interleukin-lcz (IL-1) may be able to affect the central nervous system (CNS) is by direct transport into the brain across the blood-brain barrier (BBB). The BBB of the brain consists of endothelial (between blood and interstitial fluid) and ependymal (between blood and cerebrospinal fluid) barriers. Which of these barriers IL-1 can cross has not previously been investigated. At the spinal cord, which could be the site of action for some of the effects of IL-1 such as analgesia, the BBB consists only of the endothelial barrier. 2. We show here that IL-1 labelled with 125I (I-IL) is transported across the BBB of the spinal cord by a saturable system similar to the one previously described for the brain. High performance liquid chromatography (HPLC) showed that most of the material entering the spinal cord represented intact I-IL. The BBB of the spinal cord was no more leaky to radioactively labelled albumin than the BBB of the brain and was not disrupted by 50 ug kg1 of IL-1. 3. Capillary depletion showed that most of the I-IL entered the parenchymal-interstitial fluid space of the spinal cord with only a modest amount being sequestered by the endothelial cells of its BBB. 4. I-IL entered the cervical, thoracic and lumbar regions of the spinal cord equally well.I-IL entering at the brain and diffusing caudally was estimated only to account for about 1% of the total radioactivity found in the spinal cord after i.v. injection. These results show that I-IL is able to cross the endothelial part of the BBB and that bloodborne IL-1 has direct access to the spinal cord.Interleukin-loc (IL-1) and other cytokines play major roles in the co-ordination of the neuroimmune axis (PlataSalaman, 1991). Several possible mechanisms (Breder,

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Action site of circulating interleukin-1 on the rabbit brain

Cited by 84 publications

References 19 publications

Cytokine signals propagate through the brain

Cytokine signals propagate through the brain

Neuroinflammation in Hepatic Encephalopathy: Mechanistic Aspects

Blood‐borne interleukin‐1 alpha is transported across the endothelial blood‐spinal cord barrier of mice.

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