IL-17 and related cytokines involved in the pathology and immunotherapy of multiple sclerosis: Current and future developments

Luchtman, Dirk; Ellwardt, Erik; Larochelle, Catherine; Zipp, Frauke

doi:10.1016/j.cytogfr.2014.07.013

Cited by 113 publications

(89 citation statements)

References 178 publications

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“…The present study was specifically designed to discern the possible existence of subgroups of patients with RRMS depending on their gender, age, disease stage (relapsing or remitting), time of disease evolution and response to different treatments based on the serum levels of three cytokines, IFN-γ, IL-10 and IL-17A, which helped to monitor the activity of the main T-cell subpopulations involved in the pathophysiology of MS [11,21,22]. …”

Section: Discussionmentioning

confidence: 99%

Interleukin-17A Levels Vary in Relapsing-Remitting Multiple Sclerosis Patients in Association with Their Age, Treatment and the Time of Evolution of the Disease

Guerrero-García¹,

Castañeda-Moreno

Torres-Carrillo

et al. 2015

Neuroimmunomodulation

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Objective: The present study was specifically designed to discern the possible existence of subgroups of patients with the relapsing-remitting form of multiple sclerosis (RRMS) depending on their gender, age, disease stage (relapsing or remitting), time of disease evolution and response to different treatments. Methods: We analyzed samples from patients with RRMS (50 females and 32 males) and healthy individuals (25 matched for age and gender) and determined serum concentrations of IFN-γ, IL-10 and IL-17A. We stratified patients by gender, age, treatment and disease evolution time, and subsequently correlated these independent variables with the concentrations of the previously mentioned cytokines. Results: We provided initial evidence that treatment exerted possible differential effects depending on the time of disease duration. Results evidence the existence of different subgroups of patients with MS, who can be classified as follows: (a) male or female under or over 40 years of age; (b) disease duration according to treatment (under or over 8 years of disease); (c) classification according to fluctuating levels of IFN-γ, IL-10 and IL-17A in the following three stages of disease evolution: <5 years, between 5 and 10 years, and >10 years. Conclusion: These subgroups must be taken into account for the clinical follow-up of patients with MS in order to provide them with a better and more personalized treatment, and also for a deep and detailed analysis of progressive disease, in an attempt to comprehend fluctuations and clinical variability by means of a better understanding of intrinsically physiological variables of the disease.

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Section: Discussionmentioning

confidence: 99%

Interleukin-17A Levels Vary in Relapsing-Remitting Multiple Sclerosis Patients in Association with Their Age, Treatment and the Time of Evolution of the Disease

Guerrero-García¹,

Castañeda-Moreno

Torres-Carrillo

et al. 2015

Neuroimmunomodulation

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“…10 IFN-γ-secreting T H 1 cells and interleukin (IL) 17-secreting T H 17 cells are present in MS lesions in the CNS and are known to be integral in the pathogenesis of MS in human and mouse models. [11][12][13][14] Conversely, addition of Tregs in experimental autoimmune encephalomyelitis (EAE), a mouse model simulating MS, shows a tolerogenic effect, whereas depletion of Tregs increases symptom severity. 15 This differentiation of T H cells is initiated by the interactions between naïve CD4 + T-cell populations and antigen-presenting cells (APCs), primarily dendritic cells (DCs).…”

Section: Multiple Sclerosis (Ms) Is a Neurodegenerative Disease Charamentioning

confidence: 99%

Involvement of Immune Regulation in Multiple Sclerosis

Spagnuolo

Piavis

Williams

2017

Immunol Immunogenet Insights

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Multiple sclerosis (MS) is a neurodegenerative disease characterized by neuroinflammation and demyelination that results in axon loss. Multiple sclerosis has been shown to be the result of an autoimmune response caused by a mixture of genetic and environmental factors. Dendritic cells are prominent antigen-presenting cells that interact with various molecules to regulate the immune system. The dysfunction of various features of immune regulation, including interleukins (ILs), CD4 + T cells, and suppressor of cytokine signaling (SOCS1), has been implicated in the pathogenesis of MS. T cells, particularly through the malfunction of B7-costimulatory pathways, have been shown to affect the progression of the disease. SOCS1 is important in regulating the function of T cells through its interactions with other nearby genes, especially CLEC16A, with abnormal decreases in SOCS1 expression leading to the exhibition of MS symptoms. The activation of IL-23 receptors on CD4 + T cells is pivotal to their differentiation into pathogenic T H 17 cells. Several promising compounds that downregulate gene expression of IL-23 and IL-23R have been discovered but require further investigation for efficacy and safety. Given their role in the severity and progression of MS, therapies that decrease these dysregulations may ultimately decrease symptoms and in turn improve patients' quality of life.

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“…The use of lenercept, a TNF-neutralizing molecule, in a clinical trial of patients with MS increased relapses compared with placebo. This led to investigation of dual nature of TNF that can be inflammatory or anti-inflammatory depending on patter of expression [41].…”

Section: Demeylinating Disease Multiple Sclerosis (Ms)mentioning

confidence: 99%

Cytokine Therapies in Neurological Disease

Azodi

Jacobson

2016

Neurotherapeutics

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Cytokines are a heterogeneous group of glycoproteins that coordinate physiological functions. Cytokine deregulation is observed in many neurological diseases. This article reviews current research focused on human clinical trials of cytokine and anticytokine therapies in the treatment of several neurological disease including stroke, neuromuscular diseases, neuroinfectious diseases, demyelinating diseases, and neurobehavioral diseases. This research suggests that cytokine therapy applications may play an important role in offering new strategies for disease modulation and treatment. Further, this research provides insights into the causal link between cytokine deregulation and neurological diseases.

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IL-17 and related cytokines involved in the pathology and immunotherapy of multiple sclerosis: Current and future developments

Cited by 113 publications

References 178 publications

Interleukin-17A Levels Vary in Relapsing-Remitting Multiple Sclerosis Patients in Association with Their Age, Treatment and the Time of Evolution of the Disease

Interleukin-17A Levels Vary in Relapsing-Remitting Multiple Sclerosis Patients in Association with Their Age, Treatment and the Time of Evolution of the Disease

Involvement of Immune Regulation in Multiple Sclerosis

Cytokine Therapies in Neurological Disease

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