Intravenous immunoglobulin preparation attenuates neurological signs in rat experimental autoimmune neuritis with the suppression of macrophage inflammatory protein -1α expression

Kajii, Masahiko; Kobayashi, Fujio; Kashihara, Junichi; Yuuki, Takashi; Kubo, Yoshiji; Nakae, Takashi; Kamizono, Akihito; Kuzumoto, Yoshimasa; Kusunoki, Susumu

doi:10.1016/j.jneuroim.2013.10.011

Cited by 22 publications

(18 citation statements)

References 24 publications

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“…However the efficacy of these compounds in GBS patients has been hampered by the limited number of clinical studies carried out with compounds and drugs that have been successfully used in the preclinical setting. It is however of interest that as much as human GBS benefit from IvIg, rat EAN can also be ameliorated by IvIg (Kajii et al, 2014). In addition, anecdotal reports by ourselves and others have demonstrated a rapid and clear response of GBS patients to fusidic acid, that ameliorated EAN (Nicoletti et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Decitabine induces regulatory T cells, inhibits the production of IFN-gamma and IL-17 and exerts preventive and therapeutic efficacy in rodent experimental autoimmune neuritis

Fagone

Mazzon

Chikovani

et al. 2018

Journal of Neuroimmunology

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Guillain-Barré syndrome (GBS) is an immune-mediated acute disorder of the peripheral nervous system. Despite treatment, there is an associated mortality and severe disability in 9 to 17% of the cases. Decitabine (DAC) is a hypomethylating drug used in myelodisplastic syndrome, that has been shown to exert immunomodulatory effects. We have evaluated the effects of DAC in two rodent models of GBS, the Experimental Allergic Neuritis (EAN). Both prophylactic and therapeutic treatment with DAC ameliorated the clinical course of EAN, increasing the numbers of thymic regulatory T cells and reducing the production of proinflammmatory cytokines. Our data suggest the possible use of decitabine for the treatment of GBS.

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Section: Discussionmentioning

confidence: 99%

Decitabine induces regulatory T cells, inhibits the production of IFN-gamma and IL-17 and exerts preventive and therapeutic efficacy in rodent experimental autoimmune neuritis

Fagone

Mazzon

Chikovani

et al. 2018

Journal of Neuroimmunology

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“…For instance, it is highly expressed in lesions of multiple sclerosis (MS) [22][23][24] and similarly in an animal model of MS, experimental allergic encephalomyelitis (EAE), where the onset of the disease coincides with the mRNA expression of CCL3 [25]. In the peripheral nervous system, CCL3 is upregulated in autoimmune neuritis [26] and after nerve injury [27,28]. CCL3 has been shown to be upregulated after SCI in both mice and rats [29][30][31].…”

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confidence: 99%

CCL3 contributes to secondary damage after spinal cord injury

Pelisch

Almanza

Stehlik

et al. 2020

Preprint

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Background: Secondary damage after spinal cord injury (SCI) is characterized by a cascade of events including hemorrhage, apoptosis, oxidative stress and inflammation which increase the lesion size which can influence the functional impairment. Thus, identifying specific mechanisms attributed to secondary injury is critical in minimizing tissue damage and improving neurological outcome. In this work, we are investigating the role of CCL3 (Macrophage inflammatory protein 1- α, MIP-1α), a chemokine involved in the recruitment of inflammatory cells, which plays an important role in inflammatory conditions of the central and peripheral nervous system. Methods: A mouse model of lower thoracic (T11) spinal cord contusion injury was used. We assessed expression levels of CCL3 and its receptors on the mRNA and protein level and analyzed changes in locomotor recovery and the inflammatory response in the injured spinal cord of wild-type and CCL3-/- mice.Results: The expression of CCL3 and its receptors is increased after thoracic contusion SCI in mice. We then examined the role of CCL3 after SCI and its direct influence on the inflammatory response, locomotor recovery and lesion size using CCL3 −/− mice. CCL3 −/− mice showed mild but significant improvement of locomotor recovery and a smaller lesion size compared to wild-type controls. In addition, neutrophil numbers as well as the pro-inflammatory cytokines and chemokines, known to play a deleterious role after SCI, were markedly reduced in the absence of CCL3 .Conclusion: We have identified CCL3 as a potential target to modulate the inflammatory response and secondary damage after SCI. Collectively, this study shows that the absence of CCL3 can contribute to reduced tissue damage and better functional recovery during secondary injury after SCI.

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“…To explain these seemingly inconsistent observations, we hypothesize that IVIg does not affect NK cells, but does suppress chemokine secretion by chemokine-producing cells in the uterus. Our group previously reported that IVIg improved the disease course in model mice of both systemic sclerosis [52] and chronic inflammatory demyelinating polyneuropathy [53] by suppressing chemokines. In this study, the time lag between IVIg administration and onset of effect can be explained as follows: upon intraperitoneal injection of LPS, some chemokine-producing cells in the uterus start to secrete chemokines, and after LPS injection, the concentration of chemokines rapidly reaches a level sufficient to induce CD44 bright or pathogenic NK cells to migrate, resulting in the increase in these cells in the uterus.…”

Section: Discussionmentioning

confidence: 98%

Intravenous Immunoglobulin Suppresses Abortion Relates to an Increase in the CD44bright NK Subset in Recurrent Pregnancy Loss Model Mice

Tanaka¹,

Kitashoji²,

Fukunaga³

et al. 2016

Biology of Reproduction

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Recurrent pregnancy loss (RPL), which mostly is of unknown etiology (unexplained RPL, uRPL), is defined as three or more consecutive spontaneous abortions. Some women with uRPL display a higher fraction and cytotoxicity of natural killer (NK) cells in the periphery and endometrium. Therefore, some uRPL cases have been explained by autoimmune abnormalities. The efficacy of intravenous immunoglobulin (IVIg) for uRPL has been confirmed in several clinical trials; however, its mechanism remains unknown, mainly because the abortion mechanism remains to be elucidated. In the present study, we analyzed the mechanisms of both abortion and IVIg action using a uRPL mouse model in which abortion was induced by lipopolysaccharide injection. IVIg attenuated the abortion rate in the uRPL model mice. The suppressive effect of IVIg was maximized by high dose administration early after lipopolysaccharide injection. Specifically, we discovered the presence of two distinct uterine NK (uNK) subsets: CD44(bright) and CD44(mid) In uRPL model mice, we observed an increase in the number of CD44(bright) uNK cells, while the CD44(mid) uNK subset remained unchanged. Furthermore, when abortion was reduced by IVIg administration, the cell number of the CD44(bright) uNK subset did not increase, which might allow differentiating pathological from normal uNK cells based on CD44 expression. Based on these results, we propose not only an effective administration protocol of IVIg to the uRPL model mice, but also a novel mechanism of abortion related to the increase in the CD44(bright) subset and of IVIg, which suppresses the increase of the CD44(bright) subset.

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Intravenous immunoglobulin preparation attenuates neurological signs in rat experimental autoimmune neuritis with the suppression of macrophage inflammatory protein -1α expression

Cited by 22 publications

References 24 publications

Decitabine induces regulatory T cells, inhibits the production of IFN-gamma and IL-17 and exerts preventive and therapeutic efficacy in rodent experimental autoimmune neuritis

Decitabine induces regulatory T cells, inhibits the production of IFN-gamma and IL-17 and exerts preventive and therapeutic efficacy in rodent experimental autoimmune neuritis

CCL3 contributes to secondary damage after spinal cord injury

Intravenous Immunoglobulin Suppresses Abortion Relates to an Increase in the CD44bright NK Subset in Recurrent Pregnancy Loss Model Mice

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