Intranasal administration of human IL-6 increases the severity of chemically induced seizures in rats

Kalueff, Allan V.; Lehtimäki, Kai; Ylinen, Aarne; Honkaniemi, Jari; Peltola, Jukka

doi:10.1016/j.neulet.2004.04.061

Cited by 109 publications

(78 citation statements)

References 34 publications

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“…Moreover, i.n. instillation of recombinant cytokines including IL-6 and IL-12 have been shown to affect the course of experimentally induced neurological disorders in rats (Kalueff et al, 2004;Pelidou et al, 2000). Although the mechanisms on how cytokines applied i.n.…”

Section: Discussionmentioning

confidence: 99%

Intranasal Immune Challenge Induces Sex-Dependent Depressive-Like Behavior and Cytokine Expression in the Brain

Tonelli

Holmes

Postolache

2007

Neuropsychopharmacol

116

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The association between activation of the immune system and mood disorders has been reported by several studies. However, the mechanisms by which the immune system affects mood are only partially understood. In the present study, we detected depressive-like behavior in a rat animal model which involves the induction of inflammation in the nasal cavities by intranasal (i.n.) instillation of bacterial lipopolysaccharides (LPS). Female rats showed depressive-like behavior as evidenced by the forced swim test after repeated i.n. administration of LPS. These responses were not paralleled by alterations in motor activity as measured by the open field test. In the same animals, corticosterone responses after the swimming sessions were the highest of all the groups evaluated. Real-time RT PCR was used to analyze the transcriptional regulation of the cytokines interleukin-1b, tumor necrosis factor-a, and interleukin-6 in several brain regions. Increased tumor necrosis factor-a was detected in the hippocampus and brainstem of female rats challenged with i.n. LPS. These results suggest that peripheral inflammation in the upper respiratory tract is an immune challenge capable of inducing depressive-like behavior, promoting exaggerated glucocorticoid responses to stress, and increasing cytokine transcription in the brain. These results further our understanding of the role that the immune system may play in the pathophysiology of depression.

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Section: Discussionmentioning

confidence: 99%

Intranasal Immune Challenge Induces Sex-Dependent Depressive-Like Behavior and Cytokine Expression in the Brain

Tonelli

Holmes

Postolache

2007

Neuropsychopharmacol

116

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“…Microglial cell versus macrophage cytokine production. Both TNF-␣ and IL-6 cause the amplification of proinflammatory signals within the CNS, which can lead to neuronal excitability and its related neuropathology (16,(33)(34)(35). To determine if microglia and/or macrophages produce these cytokines following infection, cells were isolated from the brains of mock-and TMEVinfected GFP chimeric mice on day 3 p.i., and ex vivo ICS staining was performed for TNF-␣ and IL-6 (Fig.…”

Section: Cd11bmentioning

confidence: 99%

Infiltrating Macrophages Are Key to the Development of Seizures following Virus Infection

Cusick

Libbey

Patel

et al. 2013

J Virol

100

173

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b Viral infections of the central nervous system (CNS) can trigger an antiviral immune response, which initiates an inflammatory cascade to control viral replication and dissemination. The extent of the proinflammatory response in the CNS and the timing of the release of proinflammatory cytokines can lead to neuronal excitability. Tumor necrosis factor alpha (TNF-␣) and interleukin-6 (IL-6), two proinflammatory cytokines, have been linked to the development of acute seizures in Theiler's murine encephalomyelitis virus-induced encephalitis. It is unclear the extent to which the infiltrating macrophages versus resident CNS cells, such as microglia, contribute to acute seizures, as both cell types produce TNF-␣ and IL-6. In this study, we show that following infection a significantly higher number of microglia produced TNF-␣ than did infiltrating macrophages. In contrast, infiltrating macrophages produced significantly more IL-6. Mice treated with minocycline or wogonin, both of which limit infiltration of immune cells into the CNS and their activation, had significantly fewer macrophages infiltrating the brain, and significantly fewer mice had seizures. Therefore, our studies implicate infiltrating macrophages as an important source of IL-6 that contributes to the development of acute seizures.

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“…An ageassociated rise in IL-6 is linked to lymphoproliferative disorders, multiple myeloma, osteoporosis, and AD (3). Furthermore, overexpression of IL-6 in the brain establishes a state permissive for the onset of neurodegenerative disease (316, 444,445). Although IL-6 levels do not appear to change in the hypothalamus, concentrations of IL-6 in the cerebellum, cerebral cortex, and hippocampus of mice increase with age (316).…”

Section: J Estradiol and Inflammatory Responses In The Cnsmentioning

confidence: 99%

Molecular Endocrinology and Physiology of the Aging Central Nervous System

2005

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Aging is associated with a progressive decline in physical and cognitive functions. The impact of age-dependent endocrine changes regulated by the central nervous system on the dynamics of neuronal behavior, neurodegeneration, cognition, biological rhythms, sexual behavior, and metabolism are reviewed. We also briefly review how functional deficits associated with increases in glucocorticoids and cytokines and declining production of sex steroids, GH, and IGF are likely exacerbated by age-dependent molecular misreading and alterations in components of signal transduction pathways and transcription factors. (Endocrine Reviews 26: 203-250, 2005)

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Intranasal administration of human IL-6 increases the severity of chemically induced seizures in rats

Cited by 109 publications

References 34 publications

Intranasal Immune Challenge Induces Sex-Dependent Depressive-Like Behavior and Cytokine Expression in the Brain

Intranasal Immune Challenge Induces Sex-Dependent Depressive-Like Behavior and Cytokine Expression in the Brain

Infiltrating Macrophages Are Key to the Development of Seizures following Virus Infection

Molecular Endocrinology and Physiology of the Aging Central Nervous System

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