Elevated serum levels of IFN-γ, IL-4 and TNF-α/unelevated serum levels of IL-10 in patients with demyelinating diseases during the acute stage

Hohnoki, K; Inoue, Akira; Koh, Chang−Sung

doi:10.1016/s0165-5728(98)00053-8

Cited by 102 publications

(58 citation statements)

References 47 publications

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“…Following methylprednisolone treatment, IL-10 serum concentrations as well as mRNA expression increased, in contrast to decreased mRNA expression of TNF-alpha and IFN-gamma, with a peak after 48 h [8]. However, in our study, as reported by others [15], both IL-4 and IL-10 serum concentrations were increased following CS treatment. In addition, proinflammatory levels of TNF-alpha and IFN-gamma concentrations were reduced in our study, mediated by CS [2].…”

Section: Discussionsupporting

confidence: 53%

“…The assessment of cytokines in untreated patients over a period of 7 years generally showed normal concentrations for all cytokines measured. In these untreated patients, no early signs of activation were found preceding relapses, such as increased IL-1, IL-2, IL-4, IL-6, TNF-alpha or IFN-gamma [10,11,15,16]. However, two patients received immune-modulating glatiramer acetate and one IFN-beta 1b, due to recurrent relapses.…”

Section: Discussionmentioning

confidence: 99%

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Benign Multiple Sclerosis Is Characterized by a Stable Neuroimmunologic Network

Haase

Faustmann

2004

Neuroimmunomodulation

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Objectives: Patients diagnosed with multiple sclerosis (MS) but without disability (Expanded Disability Status Scale score <2) form a specific group within those patients suffering from relapsing-remitting MS. Several neuroimmunologic effectors, including cytokines and melatonin, are known for their influence on the initiation of relapses and progression of the disease. Methods: We evaluated 41 female patients with benign MS with respect to their clinical course, treatments and neuroimmunological parameters, including cytokines and melatonin. One subgroup was followed up for 7 years, and another group was evaluated during acute clinical relapse. Results: The benign MS course in this homogeneous group of young patients was demonstrated by mild disease progression in 16% over 7 years. Initially, patients treated with azathioprine (AZA) revealed significantly reduced melatonin serum levels (p = 0.04) compared to untreated patients, but not at follow-up. During acute relapse, treatment with corticosteroids (CS) resulted in increased levels of type 2 cytokines as well as reduced type 1 cytokine levels. Conclusions: Our study supports the functional role of CS acting as an antiinflammatory protagonist during MS relapse, by inducing a shift towards predominance of type 2 cytokines. AZA showed a more subtle modulation of immune functions, reflected by reduced levels of the immune active hormone melatonin. During follow-up, it became apparent that stabilized levels of the interacting Th1/Th2-derived cytokines and melatonin are maintained in concordance with the benign course of MS. These findings are in accordance with the hypothesis that benign MS is characterized by a balanced cytokine and neuroendocrine network, which is supported by immune-modulating therapies.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Benign Multiple Sclerosis Is Characterized by a Stable Neuroimmunologic Network

Haase

Faustmann

2004

Neuroimmunomodulation

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“…IFN-␥ and other proinflammatory cytokines such as TNF-␣ and IL-1 have been proposed to play a critical role in the process leading to nerve damage in patients with GBS or CIDP (33)(34)(35)(36)(37)(38). Analysis of serum levels of different cytokines suggested that the relative amount of Th1 vs Th2 cytokines generally correlates with the clinical stage of disease in GBS and CIDP (39 -41).…”

Section: Discussionmentioning

confidence: 99%

Distinct Effector Mechanisms in the Development of Autoimmune Neuropathy versus Diabetes in Nonobese Diabetic Mice

Bour-Jordan

Thompson

Bluestone

2005

The Journal of Immunology

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NOD mice deficient for the costimulatory molecule B7-2 (NOD-B7-2KO mice) are protected from autoimmune diabetes but develop a spontaneous autoimmune peripheral neuropathy that resembles human diseases Guillain-Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy. Similar observations have now been made in conventional NOD mice. We have shown previously that this disease was mediated by autoreactive T cells inducing demyelination in the peripheral nervous system. In this study, we analyzed the molecular pathways involved in the disease. Our data showed that neuropathy developed in the absence of perforin or fas, suggesting that classic cytotoxicity pathways were dispensable for nerve damage in NOD-B7-2KO mice. In contrast, IFN-γ played an obligatory role in the development of neuropathy as demonstrated by the complete protection from disease and infiltration in the nerves in NOD-B7-2KO mice deficient for IFN-γ. This result was consistent with the inflammatory phenotype of T cells infiltrating the peripheral nerves. Importantly, the relative role of perforin, fas, and IFN-γ appears completely different in autoimmune diabetes vs neuropathy. Thus, there are sharp contrasts in the pathogenesis of autoimmune diseases targeting different tissues in the same NOD background.

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“…Systemic administration of recombinant rat IFN-c (rrIFN-c) worsens EAN rats and IFN-c receptor deficient mice showed a suppression of EAN [28]. In GBS patients, serum IFN-c was found elevated [29]. Although a significantly increased antigen specific peripheral blood mononuclear cells (PBMC) proliferation was not shown, PBMC secreting IFN-c spontaneously elevated in 25% of patients of GBS, which indicated a role of T cells in the immunopathology of GBS [30].…”

Section: Cytokine In Gbs and Eanmentioning

confidence: 99%

“…In GBS, although serum IL-10 is un-elevated [29], IL-10-secreting BMNC increased during the acute phase, which may account for the self-limited clinical course of GBS [29,83]. On the other hand, Myhr et al [142] reported that GBS is related to IL-10 promoter polymorphisms and IL-10 worsens the disease via enhancing the ganglioside antibody production probably.…”

Section: Il-10mentioning

confidence: 99%

The role of cytokines in Guillain–Barré syndrome

Zhu

2010

J Neurol

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Cytokines play an important role in the pathogenesis of autoimmune diseases including Guillain-Barré syndrome (GBS) and its animal model experimental autoimmune neuritis (EAN). In this article, we reviewed the current knowledge of the role of cytokines such as TNF-α, IFN-γ, IL-1β, IL-6, IL-12, IL-18, IL-23, IL-17, IL-10, IL-4 and chemokines in GBS and EAN as unraveled by studies both in the clinic and the laboratory. However, these studies occasionally yield conflicting results, highlighting the complex role that cytokines play in the disease process. Efforts to modulate cytokine function in GBS and other autoimmune disease have shown efficiency indicating that cytokines are important therapeutic targets.

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Elevated serum levels of IFN-γ, IL-4 and TNF-α/unelevated serum levels of IL-10 in patients with demyelinating diseases during the acute stage

Cited by 102 publications

References 47 publications

Benign Multiple Sclerosis Is Characterized by a Stable Neuroimmunologic Network

Benign Multiple Sclerosis Is Characterized by a Stable Neuroimmunologic Network

Distinct Effector Mechanisms in the Development of Autoimmune Neuropathy versus Diabetes in Nonobese Diabetic Mice

The role of cytokines in Guillain–Barré syndrome

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