Current Status of the Immunomodulation and Immunomediated Therapeutic Strategies for Multiple Sclerosis

Chen, Shyi-Jou; Wang, Aline Yen Ling; Fan, Hueng-Chuen; Lo, Wen-Tsung; Wang, Chih‐Chien; Sytwu, Huey‐Kang

doi:10.1155/2012/970789

Cited by 37 publications

(32 citation statements)

References 180 publications

(205 reference statements)

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“…Evidence of the immunological pathogenesis of the disease is derived from animal models of the disease, the experimental allergic encephalomyelitis, and from the efficacy of treatments targeting the presumed immunological dysfunctions at different levels [2, 3]. However, in recent years, a new potential mechanism has been proposed to contribute to the pathogenesis of MS: the presence of presumably abnormal venous hemodynamics leading to cerebral venous congestion.…”

Section: Introductionmentioning

confidence: 99%

Italian multicentre observational study of the prevalence of CCSVI in multiple sclerosis (CoSMo study): rationale, design, and methodology

et al. 2013

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Chronic cerebro-spinal venous insufficiency (CCSVI) has been proposed as a “congenital malformation” implicated in the pathogenesis of multiple sclerosis (MS). However, numerous studies failed to confirm its presence in MS patients. This paper presents the rationale, design, and methodology adopted in the CoSMo study, conducted with the aim of verifying whether or not CCSVI is linked to MS. The primary endpoint of the CoSMo study is to compare the prevalence of CCSVI in patients with MS versus patients affected by other neurodegenerative diseases (OND) and healthy volunteers. CoSMo is a multicenter, blinded, prevalence study recruiting 2,000 adult subjects, involving 43 MS centers across Italy. Assessment of the presence or absence of CCSVI is performed by color-coded duplex (CCD) sonography and two out of the five criteria according to Zamboni are necessary for the diagnosis of CCSVI. Local CCD examination carried out by a certified sonologist and the central image readings performed by experts in the field are blinded. An advanced protocol is also described in this paper. The application of a rigorous methodological design will definitively confirm whether an association exists between CCSVI and MS. Should an association be observed, this study also further examines the link between CCSVI and the severity of MS. The addition of subgroups without MS and OND also provides information on whether CCSVI is specific to MS only. Results from the CoSMo study will play a crucial role in the possible studies concerning the potential treatment of CCSVI in MS.

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Section: Introductionmentioning

confidence: 99%

Italian multicentre observational study of the prevalence of CCSVI in multiple sclerosis (CoSMo study): rationale, design, and methodology

et al. 2013

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“…MS is thought to be driven by both the T helper (Th) 1 and Th17 subsets of CD4 + T cells [reviewed in (Chen et al 2012; Jadidi-Niaragh and Mirshafiey 2011)]. Likewise, the disease induced by TMEV infection appears to be partly dependent on CD4 + T cells [reviewed in (Tsunoda and Fujinami 1996)], and both the Th1 and Th17 subsets have been implicated in disease development following TMEV infection of susceptible mouse strains (Hou et al 2009; Pullen et al 1994).…”

Section: Introductionmentioning

confidence: 99%

Possible role of interleukin-17 in a prime/challenge model of multiple sclerosis

2012

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No one single pathogen has been identified as the causative agent of multiple sclerosis (MS). Alternately, the likelihood of an autoimmune event may be nonspecifically enhanced by different infectious agents. In a novel animal model of MS, SJL/J mice primed through infection with a recombinant vaccinia virus (VV) encoding myelin proteolipid protein (PLP) (VVPLP) were susceptible to a central nervous system (CNS) inflammatory disease following administration of a nonspecific immunostimulant [complete Freund's adjuvant (CFA) plus Bordetella pertussis (BP)]. Mononuclear cells isolated from the brains, but not the spleens, of VVPLP-primed CFA/BP challenged mice produced interleukin (IL)-17 and interferon-γ and transferred a CNS inflammatory disease to naïve SJL/J mice. Administration of curdlan, a T helper 17 cell inducer, unexpectedly resulted in less severe clinical and histological signs of disease, compared to CFA/BP challenged mice, despite the induction of IL-17 in the periphery. Further examination of the VVPLP-prime CFA/BP challenge model may suggest new mechanisms for how different pathogens associated with MS can protect or enhance disease.

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“…However, our results extend previous studies showing that Cannabis use may globally suppress cytokine production. IL17-producing T-cells (T H 17) are important players in a number of autoimmune processes and IL17 is considered to be a key player in the cytokine milieu in patients with MS, a putative biomarker for disease activity, and predictor of drug response in MS (Axtell, de Jong et al 2010, Hecker, Paap et al 2011, Li, Wang et al 2011, Chen, Wang et al 2012) (Frisullo, Nociti et al 2008, Kallaur, Oliveira et al 2013, Kozela, Juknat et al 2013). Notable in this study is the global suppression of IL17 in subjects who are exposed to Cannabis, as cannabinoids were shown elsewhere to decrease the Th17-associated autoimmune phenotype (Kozela, Juknat et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Cannabis use by individuals with multiple sclerosis: effects on specific immune parameters

et al. 2014

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Cannabinoids affect immune responses in ways that may be beneficial for autoimmune diseases. We sought to determine whether chronic Cannabis use differentially modulates a select number of immune parameters in healthy controls and individuals with multiple sclerosis (MS cases). Subjects were enrolled and consented to a single blood draw, matched for age and BMI. We measured monocyte migration isolated from each subject, as well as plasma levels of endocannabinoids and cytokines. Cases met definition of MS by international diagnostic criteria. Monocyte cell migration measured in control subjects and individuals with MS were similarly inhibited by a set ratio of phytocannabinoids. The plasma levels of CCL2 and IL17 were reduced in non-naïve cannabis users irrespective of the cohorts. We detected a significant increase in the endocannabinoid arachidonoylethanolamine (AEA) in serum from individuals with MS compared to control subjects, and no significant difference in levels of other endocannabinoids and signaling lipids irrespective of Cannabis use. Chronic Cannabis use may affect the immune response to similar extent in individuals with MS and control subjects through the ability of phytocannabinoids to reduce both monocyte migration and cytokine levels in serum. From a panel of signaling lipids, only the levels of AEA are increased in individuals with MS, irrespective from Cannabis use or not. Our results suggest that both MS cases and controls respond similarly to chronic Cannabis use with respect to the immune parameters measured in this study.

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Current Status of the Immunomodulation and Immunomediated Therapeutic Strategies for Multiple Sclerosis

Cited by 37 publications

References 180 publications

Italian multicentre observational study of the prevalence of CCSVI in multiple sclerosis (CoSMo study): rationale, design, and methodology

Italian multicentre observational study of the prevalence of CCSVI in multiple sclerosis (CoSMo study): rationale, design, and methodology

Possible role of interleukin-17 in a prime/challenge model of multiple sclerosis

Cannabis use by individuals with multiple sclerosis: effects on specific immune parameters

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