Decreased production of TNF-alpha by lymph node cells indicates experimental autoimmune encephalomyelitis remission in Lewis rats

Seger, Juliana; Zorzella-Pezavento, Sofia Fernanda Gonçalves; Pelizon, A. C.; Martins, Denizar Cruz; Domingues, Alexandre; Sartori, Alexandrina

doi:10.1590/s0074-02762010000300004

Cited by 14 publications

(9 citation statements)

References 38 publications

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“…At 7 days post immunization (dpi), immunized rats started to exhibit clinical symptoms of EAE including the loss of tail tonicity, abnormal gait, and continuous progression of disease. At around 15 to 18 dpi, animals showed scoring up to grade 4 and exhibited features such as hind leg paralysis and hind body paralysis with physical symptoms of reddish and swollen hind feet [ 33 ] ( Fig 3A ).…”

Section: Resultsmentioning

confidence: 99%

The Synergistic Local Immunosuppressive Effects of Neural Stem Cells Expressing Indoleamine 2,3-Dioxygenase (IDO) in an Experimental Autoimmune Encephalomyelitis (EAE) Animal Model

Lee

et al. 2015

PLoS ONE

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Neurodegenerative diseases provoke robust immunological reactions in the central nervous system (CNS), which further deteriorate the neural tissue damage. We hypothesized that the expression levels of indoleamine 2,3-dioxygenase (IDO), an enzyme that has potent immune suppressive activities, in neural stem cells (NSCs) would have synergistic therapeutic effects against neurodegenerative diseases, since NSCs themselves have low IDO expression. In this study, the synergistic immune suppressive effects of rat fetal NSCs expressing IDO (rfNSCs-IDO) were validated by mixed leukocyte reaction (MLR) in vitro and an experimental autoimmune encephalomyelitis (EAE) animal model in vivo. rfNSCs-IDO showed significantly more suppressive effects on T cell proliferation in the MLR compared to control rfNSCs (rfNSCs-Cont). Importantly, IDO inhibition using 1-methyl-DL-tryptophan (1-MT), an IDO inhibitor, reversed the synergistic effects, confirming IDO-specific effects in rfNSCs-IDO. In the EAE animal model, systemic rfNSCs-IDO injections resulted in significant local immune suppression in the cervical lymph nodes and CNS, evidenced by a reduction in the number of activated T lymphocytes and an increase in regulatory T cell numbers, which induced significantly fewer clinical symptoms and faster recovery. In contrast, rfNSCs-Cont failed to reduce symptoms in the EAE animal models, although they showed local immune suppression, which was significantly less than that in rfNSCs-IDO. Taken together, IDO expression in NSCs synergistically potentiates the immune suppression activities of NSCs and could be applicable for the development of therapeutic modalities against various neurodegenerative diseases.

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Section: Resultsmentioning

confidence: 99%

The Synergistic Local Immunosuppressive Effects of Neural Stem Cells Expressing Indoleamine 2,3-Dioxygenase (IDO) in an Experimental Autoimmune Encephalomyelitis (EAE) Animal Model

Lee

et al. 2015

PLoS ONE

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“…Subsequent to the deficits observed during the initial acute attack, most of the animals recorded at the firstremission phase of EAE in our study demonstrated an increase in amplitude in both teriflunomide-treated groups. During the remission phase of EAE, it has been reported that numerous regenerative and cell repair processes occur after the proinflammatory phase of EAE, and these processes work to repair or enhance the survival of affected neurons (Zhu et al, 2003;Barbizan and Oliveira, 2010;Seger et al, 2010). However, in EAE vehicle-treated animals, we observed a reduction in amplitude at first relapse and then a more notable reduction during the relapse-remission phase of EAE disease; this time frame has been associated with increased axonal loss (Merrill et al, 2009).…”

Section: Effects Of Teriflunomide On Da Eae Rat Electrophysiology 207mentioning

confidence: 48%

Effects of Prophylactic and Therapeutic Teriflunomide in Transcranial Magnetic Stimulation–Induced Motor-Evoked Potentials in the Dark Agouti Rat Model of Experimental Autoimmune Encephalomyelitis

Iglesias-Bregna

Hanák

et al. 2013

J Pharmacol Exp Ther

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Teriflunomide is a once-daily oral immunomodulatory agent recently approved in the United States for the treatment of relapsing multiple sclerosis (RMS). This study investigated neurophysiological deficits in descending spinal cord motor tracts during experimental autoimmune encephalomyelitis (EAE; a model of multiple sclerosis) and the functional effectiveness of prophylactic or therapeutic teriflunomide treatment in preventing the debilitating paralysis observed in this model. Relapsing-remitting EAE was induced in Dark Agouti rats using rat spinal cord homogenate. Animals were treated with oral teriflunomide (10 mg/kg daily) prophylactically, therapeutically, or with vehicle (control). Transcranial magnetic motor-evoked potentials were measured throughout the disease to provide quantitative assessment of the neurophysiological status of descending motor tracts. Axonal damage was quantified histologically by silver staining. Both prophylactic and therapeutic teriflunomide treatment significantly reduced maximum EAE disease scores (P , 0.0001 and P 5 0.0001, respectively) compared with vehicle-treated rats. Electrophysiological recordings demonstrated that both teriflunomide treatment regimens prevented a delay in wave-form latency and a decrease in wave-form amplitude compared with that observed in vehicle-treated animals. A significant reduction in axonal loss was observed with both teriflunomide treatment regimens compared with vehicle (P , 0.0001 and P 5 0.0014, respectively). The results of this study suggest that therapeutic teriflunomide can prevent the deficits observed in this animal model in descending spinal cord motor tracts. The mechanism behind reduced axonal loss and improved motor function may be primarily the reduced inflammation and consequent demyelination observed in these animals through the known effects of teriflunomide on impairing proliferation of stimulated T cells. These findings may have significant implications for patients with RMS.

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“…[46][47][48] The significant point in the present study was the higher percentage of weight gain with the medium dose of MSc1 during the acute phase of disease compared to the control groups.…”

mentioning

confidence: 44%

The therapeutic effects of MSc1 nanocomplex, synthesized by nanochelating technology, on experimental autoimmune encephalomyelitic C57/BL6 mice

Fakharzadeh¹,

Sahraian²,

Hafizi³

et al. 2014

IJN

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Purpose Currently approved therapies for multiple sclerosis (MS) at best only slow down its progression. Therefore, it is necessary to utilize novel technologies in order to synthesize smart multifunctional structures. In the present study, for the first time we evaluated the therapeutic potential of MSc1 nanocomplex, which was designed based on novel nanochelating technology. Materials and methods MSc1 cell-protection capacity, with and without iron bond, was evaluated against hydrogen peroxide (H 2 O 2 )-induced oxidative stress in cultured rat pheochromocytoma-12 cells. The ability of MSc1 to maintain iron bond at pH ranges of 1–7 was evaluated. Nanocomplex toxicity was examined by estimating the intraperitoneal median lethal dose (LD 50 ). Experimental autoimmune encephalomyelitic mice were injected with MSc1 14 days after disease induction, when the clinical symptoms appeared. The clinical score, body weight, and disease-induced mortality were monitored until day 54. In the end, after collecting blood samples for assessing hemoglobin and red blood cell count, the brains and livers of the mice were isolated for hematoxylin and eosin staining and analysis of iron content, respectively. Results The results showed that MSc1 prevented H 2 O 2 -induced cell death even after binding with iron, and it preserved its bond with iron constant at pH ranges 1–7. The nanocomplex intraperitoneal LD 50 was 1,776.59 mg/kg. MSc1 prompted therapeutic behavior and improved the disabling features of experimental autoimmune encephalomyelitis, which was confirmed by decreased clinical scores versus increased body mass and 100% survival probability. It did not cause any adverse effects on hemoglobin or red blood cell count. Histopathological studies showed no neural loss or lymphocyte infiltration in MSc1-treated mice, while the hepatic iron content was also normal. Conclusion These results demonstrate that MSc1 could be a promising beneficial novel agent and has the capacity to be evaluated in further studies.

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Decreased production of TNF-alpha by lymph node cells indicates experimental autoimmune encephalomyelitis remission in Lewis rats

Abstract: Experimental autoimmune encephalomyelitis (EAE) is mediated by CD4 + Th1 cells that mainly secrete IFN-γ and TNF-α, important

Cited by 14 publications

References 38 publications

The Synergistic Local Immunosuppressive Effects of Neural Stem Cells Expressing Indoleamine 2,3-Dioxygenase (IDO) in an Experimental Autoimmune Encephalomyelitis (EAE) Animal Model

The Synergistic Local Immunosuppressive Effects of Neural Stem Cells Expressing Indoleamine 2,3-Dioxygenase (IDO) in an Experimental Autoimmune Encephalomyelitis (EAE) Animal Model

Effects of Prophylactic and Therapeutic Teriflunomide in Transcranial Magnetic Stimulation–Induced Motor-Evoked Potentials in the Dark Agouti Rat Model of Experimental Autoimmune Encephalomyelitis

The therapeutic effects of MSc1 nanocomplex, synthesized by nanochelating technology, on experimental autoimmune encephalomyelitic C57/BL6 mice

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