Expression of cytokines and cytokine receptors in the rat brain after kainic acid-induced seizures

Lehtimäki, Kai; Peltola, Jukka; Koskikallio, Elina; Keränen, Tapani; Honkaniemi, Jari

doi:10.1016/s0169-328x(02)00654-x

Cited by 142 publications

(81 citation statements)

References 48 publications

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“…Our finding showing decreased IL-1 ␤ levels after seizures seems to be in conflict with previous reports showing increased IL-1 ␤ production after seizures [6,19,13] . This discrepancy may be explained partly by the fact that the production of IL-1 ␤ may be suppressed by IL-6 and IL-1ra, similarly to peripheral tissues [20] .…”

Section: Discussioncontrasting

confidence: 99%

Levels of IL-1β and IL-1ra in Cerebrospinal Fluid of Human Patients after Single and Prolonged Seizures

Lehtimäki

Keränen²,

Palmio³

et al. 2009

Neuroimmunomodulation

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Background: Experimentally induced seizures are associated with increased production of inflammatory cytokines in the nervous system. Elevated cerebrospinal fluid levels of cytokine interleukin-6 (IL-6) have been found after a single generalized seizure in human patients. After prolonged seizures, levels of IL-6 have been shown to be even higher compared with single seizures. In the present study, we determined the levels of proconvulsive IL-1β and anticonvulsive IL-1ra in cerebrospinal fluid after single tonic-clonic seizures as well as after prolonged seizures. Methods: The levels of cytokines were measured using enzyme-linked immunosorbent assay. Results: We found that after single seizures, a slight increase in anticonvulsive IL-1ra levels was found; however, after prolonged partial or recurrent tonic-clonic seizures, the levels of IL-1ra were significantly elevated, together with decreased IL-1β levels. Conclusion: Our results indicate that after severe seizures, the balance between IL-1-type cytokines is changed towards a neuroprotective and anticonvulsive direction with an overproduction of IL-1ra with respect to potentially neurotoxic IL-1β. This reaction may serve as a defense mechanism of the nervous system against excitotoxic neuronal damage.

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Section: Discussioncontrasting

confidence: 99%

Levels of IL-1β and IL-1ra in Cerebrospinal Fluid of Human Patients after Single and Prolonged Seizures

Lehtimäki

Keränen²,

Palmio³

et al. 2009

Neuroimmunomodulation

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“…Rapid induction of IL-6 expression in the brain is known to occur in most (if not all) neuropathological conditions, including seizures in humans (Lehtimäki et al, 2003(Lehtimäki et al, , 2004Peltola et al, 1998Peltola et al, , 2002Jankowsky and Patterson, 1999) where IL-6 levels in the cerebrospinal fluid up to 100 pg/ml have been found (Peltola et al, 2000). Astrocytes are a major source of IL-6 in the brain (van Wagoner and Benveniste, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…It is known that the expression of A 1 receptors in WT mice is increased after neuropathological events, such as seizures Vanore et al, 2001;Angelatou et al, 1991Angelatou et al, , 1993. On the other hand, several reports have shown that those noxious conditions trigger the release of IL-6 (Lehtimäki et al, 2003;Peltola et al, 1998Peltola et al, , 2002. Accordingly, we used WT animals and IL-6-deficient mice to evaluate the relationship between the expression of IL-6 and the upregulation of adenosine A 1 receptors in response to PTZ-induced seizures.…”

Section: Influence Of Il-6 On Adenosine a 1 Receptors In Vivomentioning

confidence: 99%

Interleukin-6 Upregulates Neuronal Adenosine A1 Receptors: Implications for Neuromodulation and Neuroprotection

Biber

Pinto-Duarte

Wittendorp

et al. 2007

Neuropsychopharmacol

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The immunological response in the brain is crucial to overcome neuropathological events. Some inflammatory mediators, such as the immunoregulatory cytokine interleukin-6 (IL-6) affect neuromodulation and may also play protective roles against various noxious conditions. However, the fundamental mechanisms underlying the long-term effects of IL-6 in the brain remain unclear. We now report that IL-6 increases the expression and function of the neuronal adenosine A 1 receptor, with relevant consequences to synaptic transmission and neuroprotection. IL-6-induced amplification of A 1 receptor function enhances the responses to readily released adenosine during hypoxia, enables neuronal rescue from glutamate-induced death, and protects animals from chemically induced convulsing seizures. Taken together, these results suggest that IL-6 minimizes the consequences of excitotoxic episodes on brain function through the enhancement of endogenous adenosinergic signaling.

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“…It has also been supported by the demonstration of an epilepsy-induced decrease in A 1 receptor expression in chronic seizures [67,[158][159][160]228] and adaptive changes in Ado receptors after seizures [111]. Activation of A 2B receptors by elevated Ado levels may induce the release of proinflammatory interleukin-6 (IL-6) from astrocytes leading to increased expression of A 1 receptors and their functions in the brain [229,230], which may explain (i) the increase of A 1 receptor expression after seizures parallel with increasing Ado level and (ii) the higher level of IL-6 in the brain areas (e.g., in the hippocampus and cortex) of epileptic patients and rats [186,[231][232][233], which may have a protective effect against subsequent seizures [230]. In addition, an increase in A 1 receptor density has been demonstrated in the epileptic tissue, for example, in PTZ kindling mice and kainic-acid-treated rats, which may also be an adaptive/protective mechanism against hyperexcitability-induced seizures and convulsions [96,230,[234][235][236][237][238][239].…”

Section: Adenosine Receptor Agonists and Antagonistsmentioning

confidence: 99%

The Antiepileptic Potential of Nucleosides

Kovács¹,

Kékesi²,

Juhász³

et al. 2014

CMC

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Despite newly developed antiepileptic drugs to suppress epileptic symptoms, approximately one third of patients remain drug refractory. Consequently, there is an urgent need to develop more effective therapeutic approaches to treat epilepsy. A great deal of evidence suggests that endogenous nucleosides, such as adenosine (Ado), guanosine (Guo), inosine (Ino) and uridine (Urd), participate in the regulation of pathomechanisms of epilepsy. Adenosine and its analogues, together with non-adenosine (non-Ado) nucleosides (e.g., Guo, Ino and Urd), have shown antiseizure activity. Adenosine kinase (ADK) inhibitors, Ado uptake inhibitors and Ado-releasing implants also have beneficial effects on epileptic seizures. These results suggest that nucleosides and their analogues, in addition to other modulators of the nucleoside system, could provide a new opportunity for the treatment of different types of epilepsies. Therefore, the aim of this review article is to summarize our present knowledge about the nucleoside system as a promising target in the treatment of epilepsy.

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Expression of cytokines and cytokine receptors in the rat brain after kainic acid-induced seizures

Cited by 142 publications

References 48 publications

Levels of IL-1β and IL-1ra in Cerebrospinal Fluid of Human Patients after Single and Prolonged Seizures

Levels of IL-1β and IL-1ra in Cerebrospinal Fluid of Human Patients after Single and Prolonged Seizures

Interleukin-6 Upregulates Neuronal Adenosine A1 Receptors: Implications for Neuromodulation and Neuroprotection

The Antiepileptic Potential of Nucleosides

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