Approach to discriminate subgroups in multiple sclerosis with cerebrospinal fluid (CSF) basic inflammation indices and TNF-α, IL-1β, IL-6, IL-8

Kleine, T. O.; Zwerenz, Peter; Graser, Claus; Zöfel, P.

doi:10.1016/s0361-9230(03)00096-0

Cited by 27 publications

(9 citation statements)

References 78 publications

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“…Furthermore, IL-1β and IL-1ra production within the ventricular choroid plexus is in line with observations that IL-1β production within the choroid plexus is significantly increased during the early phase of EAE in mice [58]. Moreover, IL-1β [59], [60] and IL-1ra [59] protein levels are significantly enhanced in the cerebrospinal fluid (CSF) of MS patients. As the choroid plexus regulates the composition of the CSF content, it may be suggested that choroid plexus-derived IL-1β and IL-1ra are secreted into the CSF [61].…”

Section: Discussionsupporting

confidence: 88%

Interleukin-1β and Interleukin-1 Receptor Antagonist Appear in Grey Matter Additionally to White Matter Lesions during Experimental Multiple Sclerosis

et al. 2013

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BackgroundMultiple sclerosis (MS) has been mainly attributed to white matter (WM) pathology. However, recent evidence indicated the presence of grey matter (GM) lesions. One of the principal mediators of inflammatory processes is interleukin-1β (IL-1β), which is known to play a role in MS pathogenesis. It is unknown whether IL-1β is solely present in WM or also in GM lesions. Using an experimental MS model, we questioned whether IL-1β and the IL-1 receptor antagonist (IL-1ra) are present in GM in addition to affected WM regions.MethodsThe expression of IL-1β and IL-1ra in chronic-relapsing EAE (cr-EAE) rats was examined using in situ hybridization, immunohistochemistry and real-time PCR. Rats were sacrificed at the peak of the first disease phase, the trough of the remission phase, and at the peak of the relapse. Histopathological characteristics of CNS lesions were studied using immunohistochemistry for PLP, CD68 and CD3 and Oil-Red O histochemistry.ResultsIL-1β and IL-ra expression appears to a similar extent in affected GM and WM regions in the brain and spinal cord of cr-EAE rats, particularly in perivascular and periventricular locations. IL-1β and IL-1ra expression was dedicated to macrophages and/or activated microglial cells, at sites of starting demyelination. The time-dependent expression of IL-1β and IL-1ra revealed that within the spinal cord IL-1β and IL-1ra mRNA remained present throughout the disease, whereas in the brain their expression disappeared during the relapse.ConclusionsThe appearance of IL-1β expressing cells in GM within the CNS during cr-EAE may explain the occurrence of several clinical deficits present in EAE and MS which cannot be attributed solely to the presence of IL-1β in WM. Endogenously produced IL-1ra seems not capable to counteract IL-1β-induced effects. We put forward that IL-1β may behold promise as a target to address GM, in addition to WM, related pathology in MS.

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Section: Discussionsupporting

confidence: 88%

Interleukin-1β and Interleukin-1 Receptor Antagonist Appear in Grey Matter Additionally to White Matter Lesions during Experimental Multiple Sclerosis

et al. 2013

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“…In other words, during the MS course inflammatory reaction and immunological response are not limited within the CNS, but widespread. The results of recent studies 34,35 are consistent with this hypothesis. Significant and sustained increase of serum TNF-alpha was found in healthy subjects a day after a psychologically stressful event 34 .…”

Section: Discussionsupporting

confidence: 79%

Tumor necrosis factor-alfa and interleukin-4 in cerbrospinal fluid and plasma in different clinical forms of multiple sclerosis

et al. 2012

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“…We next discuss the role of IL-1β in MS and EAE. In the clinic, significantly higher values of IL-1β have been detected in the cerebrospinal fluid and serum of MS patients [ 31 ]. Several studies have provided evidence that IL-1β plays a crucial role in EAE.…”

Section: Discussionmentioning

confidence: 99%

Microsomal Prostaglandin E Synthase-1 Facilitates an Intercellular Interaction between CD4+ T Cells through IL-1β Autocrine Function in Experimental Autoimmune Encephalomyelitis

Takemiya

Takeuchi

Kawakami

2017

IJMS

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Microsomal prostaglandin synthetase-1 (mPGES-1) is an inducible terminal enzyme that produces prostaglandin E2 (PGE2). In our previous study, we investigated the role of mPGES-1 in the inflammation and demyelination observed in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, using mPGES-1-deficient (mPGES-1−/−) and wild-type (wt) mice. We found that mPGES-1 facilitated inflammation, demyelination, and paralysis and was induced in vascular endothelial cells and macrophages and microglia around inflammatory foci. Here, we investigated the role of interleukin-1β (IL-1β) in the intercellular mechanism stimulated by mPGES-1 in EAE spinal cords in the presence of inflammation. We found that the area invaded by CD4-positive (CD4+) T cells was extensive, and that PGE2 receptors EP1–4 were more induced in activated CD4+ T cells of wt mice than in those of mPGES-1−/− mice. Moreover, IL-1β and IL-1 receptor 1 (IL-1r1) were produced by 65% and 48% of CD4+ T cells in wt mice and by 44% and 27% of CD4+ T cells in mPGES-1−/− mice. Furthermore, interleukin-17 (IL-17) was released from the activated CD4+ T cells. Therefore, mPGES-1 stimulates an intercellular interaction between CD4+ T cells by upregulating the autocrine function of IL-1β in activated CD4+ T cells, which release IL-17 to facilitate axonal and myelin damage in EAE mice.

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Approach to discriminate subgroups in multiple sclerosis with cerebrospinal fluid (CSF) basic inflammation indices and TNF-α, IL-1β, IL-6, IL-8

Cited by 27 publications

References 78 publications

Interleukin-1β and Interleukin-1 Receptor Antagonist Appear in Grey Matter Additionally to White Matter Lesions during Experimental Multiple Sclerosis

Interleukin-1β and Interleukin-1 Receptor Antagonist Appear in Grey Matter Additionally to White Matter Lesions during Experimental Multiple Sclerosis

Tumor necrosis factor-alfa and interleukin-4 in cerbrospinal fluid and plasma in different clinical forms of multiple sclerosis

Microsomal Prostaglandin E Synthase-1 Facilitates an Intercellular Interaction between CD4+ T Cells through IL-1β Autocrine Function in Experimental Autoimmune Encephalomyelitis

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