Methadone diminishes neuroinflammation and disease severity in EAE through modulating T cell function

Kafami, Laya; Etesami, Ifa; Felfeli, Mina; Enayati, Neda; Ghiaghi, Roya; Aminian, Atefeh; Dehpour, Ahmad Reza

doi:10.1016/j.jneuroim.2012.10.015

Cited by 28 publications

(19 citation statements)

References 23 publications

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“…Different opioids have been reported to exert immunosuppressive and modulatory effects on a variety of immune cells, including T and B cells, macrophages and natural killer (NK) cells. Moreover, they have been shown to diminish the levels of inflammatory cytokines, including IL-2, interferon gamma (IFN-γ), and TNF-α, while enhancing the levels of anti-inflammatory cytokines like IL-4 during immune/inflammatory processes (Suo, Weber, 1998;Sacerdote, 2006;Kafami et al, 2013). Methadone (Me), for instance, a potent μ-opioid receptor agonist, has been shown to diminish neuroinflammation and severity of symptoms in experimental autoimmune encephalomyelitis (Kafami et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, they have been shown to diminish the levels of inflammatory cytokines, including IL-2, interferon gamma (IFN-γ), and TNF-α, while enhancing the levels of anti-inflammatory cytokines like IL-4 during immune/inflammatory processes (Suo, Weber, 1998;Sacerdote, 2006;Kafami et al, 2013). Methadone (Me), for instance, a potent μ-opioid receptor agonist, has been shown to diminish neuroinflammation and severity of symptoms in experimental autoimmune encephalomyelitis (Kafami et al, 2013). On the other hand, Monibi et al (2015) did not find any alteration in leucocyte TNF-α, IL-FIGURE 4 -Total count in pixels of GFAP immunoreactive astrocytes (represented as mean ± standard deviation) in the NAc from the different experimental groups (n=6 per group).…”

Section: Discussionmentioning

confidence: 99%

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Astrocytic expression of GFAP and serum levels of IL-1β and TNF-α in rats treated with different pain relievers

Amaral

Dossa

Viebig

et al. 2016

Braz. J. Pharm. Sci.

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Pro-inflammatory cytokines and glial cells, especially microglial cells, have been implicated in persistent pain sensitization. Less is known about the role of astrocytes in pain regulation. This study aimed to observe the expression of the astrocytic biomarker glial fibrillary acidic protein (GFAP) and the serum levels of interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) after short-term administration of central pain relievers in rats not submitted to noxious stimuli. Male Wistar rats were divided into five groups, receiving for nine days-(1) amitriptyline (Amt-10 mg/kg/day, by gavage); (2) gabapentin (Gb-60 mg/kg/day, by gavage; (3) methadone (Me-4.5 mg/kg/day, intraperitoneal route [IP]); (4) morphine (Mo-10 mg/kg/day, IP); or (5) 0.9% saline solution, IP. Brain samples were collected for immunohistochemical study of GFAP expression in the mesencephalon and nucleus accumbens (NAc). The area of GFAP-positive cells was calculated using MetaMorph software and serum levels of IL-1β and TNF-α were measured by enzyme-linked immunosorbent assay. Serum TNF-α levels were decreased in the groups treated with Mo, Me and Gb, but not in the Amt-treated group. IL-1β decreased only in rats treated with Me. The astrocytic expression of GFAP was decreased in the brainstem with all drugs, while it was increased in the NAc with Amt, Me and Mo.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Astrocytic expression of GFAP and serum levels of IL-1β and TNF-α in rats treated with different pain relievers

Amaral

Dossa

Viebig

et al. 2016

Braz. J. Pharm. Sci.

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“…0, no clinical sign; 0.5, partial tail paralysis; 1.0, complete tail paralysis; 1.5, complete tail paralysis and discrete hind limb weakness; 2.0, complete tail paralysis and strong hind limb weakness; 2.5, unilateral hind limb paralysis; 3, complete hind limb paralysis; 3.5, hind limb paralysis and forelimb weakness; 4.0, complete paralysis (tetraplegia), and 5.0, moribund or dead [17, 18]. The successful induction of EAE in all mice in both groups was confirmed by this scoring scale.…”

Section: Methodsmentioning

confidence: 99%

“…Three clinical parameters were analyzed to compare the course of EAE between the two groups: severity of disease with cumulative disease index, which was calculated for each mouse as the sum of the daily clinical scores for the entire duration of disease, disease onset and peak score of the disease, i.e. the highest score reached by each animal during the course of disease [18]. Having the highest clinical signs of disease without any improvement for at least three uninterrupted days was determined as an acute phase.…”

Section: Methodsmentioning

confidence: 99%

MS14 Down-regulates Lipocalin2 Expression in Spinal Cord Tissue in an Animal Model of Multiple Sclerosis in female C57BL/6

Ebrahimi-Kalan

Rad

Kafami

et al. 1996

Iranian Biomedical Journal (IBJ); ISSN 1028-852x

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“…Microglia involves in production of cytokines such as IL-6 and TNF-α, which can cause more inflammatory cytokines production by CNS-reactive CD4 (+) T-cells (5). Previous studies have demonstrated that glial cells can be the key effectors of EAE neurohistological changes (6, 27). Collectively, these data proved IL-6 as a clear target of strategic therapies such as herbal medications.…”

Section: Discussionmentioning

confidence: 99%

MS14, a Marine Herbal Medicine, an Immunosuppressive Drug in Experimental Autoimmune Encephalomyelitis

Ebrahimi-Kalan

Rad

Kafami

et al. 2014

Iran Red Crescent Med J

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Background:Cytokines are secreted signaling proteins which play essential roles in immune responses during experimental autoimmune encephalomyelitis (EAE), a demyelinating model that mimics many features of multiple sclerosis (MS). Interleukin 6 (IL-6) is a multifunctional cytokine produced by different cells, mediating inflammatory reactions and immune-mediated processes. Several studies have described immunosuppressive potentials of several herbal medicines. MS14 as an Iranian marine herbal medicine has anti-inflammatory and immunomodulatory activities.Objectives:The present study investigated the immunosuppressive potential of MS14 as an herbal drug as well as the IL-6 level in EAE model. We hope it will be a new approach for neurologic diseases and autoimmune originated diseases therapy.Patients and Methods:The present experimental study was a collaboration between Department of Anatomical Sciences of Tabriz University of Medical Sciences and Shefa Neuroscience Research Center of Tehran. We used 30 C57BL/6 mice. The animals were immunized with myelin oligodendrocyte glycoprotein (MOG) to induce EAE and treated with MS14-containing (30%) diets. Subjects were selected by simple random sampling and then they were randomly allocated to two groups. EAE symptoms were assessed using the standard 10–point EAE scoring system from the seventh to the 35th day after immunization. Afterwards, the spleen was removed and its cells were cultured with or without MOG 35-55; then, the IL-6 level was analyzed by ELISA. In addition, histopathological studies were carried out for demyelination lesion evaluation in the spinal cord.Results:MS14 significantly improved clinical symptoms of EAE compared with the control (P < 0.05). It also suppressed proliferative responses of T cells and decreased IL-6 expression (16.93 ± 2.7 vs. 21.4 ± 3.33) (P < 0.05).Conclusions:Our results strongly suggested that IL-6 as a potential molecule could have a role in neuroimmunology and neuroinflammation, which is in congruent with previous studies. Therefore, it can be a clear target in strategic therapies and support effective properties of phytotherapy in EAE and MS treatment.

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Methadone diminishes neuroinflammation and disease severity in EAE through modulating T cell function

Cited by 28 publications

References 23 publications

Astrocytic expression of GFAP and serum levels of IL-1β and TNF-α in rats treated with different pain relievers

Astrocytic expression of GFAP and serum levels of IL-1β and TNF-α in rats treated with different pain relievers

MS14 Down-regulates Lipocalin2 Expression in Spinal Cord Tissue in an Animal Model of Multiple Sclerosis in female C57BL/6

MS14, a Marine Herbal Medicine, an Immunosuppressive Drug in Experimental Autoimmune Encephalomyelitis

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