The cytokine storm in multiple sclerosis

1998 ◽  
Vol 4 (1) ◽  
pp. 12-15 ◽  
Author(s):  
Hans Link
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Immune System ◽  
Lesion Size ◽  
Disease Course ◽  
Cytokine Storm ◽  
Cytokine Network ◽  
Benign Course

MS is associated with a cytokine storm characterized by the parallel upregulation of proinflammatory (IFN-g, TNF-a, and b, and IL-12) and immune response-down-regulating (TGF-b, IL-10) cytokines. Also IL-6 and the cytolytic molecule perforin are upregulated. Even when evaluated in individual MS patients over the disease course, no Th1/Th2 dichotomy is obvious but, instead, upregulation of Th1+Th2+Th3 cytokines simultaneously, probably reflecting the complex pathology of MS in lesion size, time and distribution in the indiviual patient. Few correlations have been observed between cytokines and clinical MS variables, though upregulation of TGF-b seems to correlate with benign course and minor disability. Both pro- and antiinflammatory cytokines are also produced by microglia and astrocytes, constituting a CNS-cytokine network that interacts with the cytokine network of the immune system. This complexity is to be kept in mind when searching for cytokine abnormalities in MS.

scholarly journals Suppression of the Peripheral Immune System Limits the Central Immune Response Following Cuprizone-Feeding: Relevance to Modelling Multiple Sclerosis

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1314 ◽  
Author(s):  
Sen ◽  
Almuslehi ◽  
Gyengesi ◽  
Myers ◽  
Shortland ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Immune System ◽  
Adaptive Immune System ◽  
Synaptic Function ◽  
Adaptive Immune ◽  
Splenic Atrophy ◽  
The Impact ◽  
The Brain ◽  
Inside Out

Cuprizone (CPZ) preferentially affects oligodendrocytes (OLG), resulting in demyelination. To investigate whether central oligodendrocytosis and gliosis triggered an adaptive immune response, the impact of combining a standard (0.2%) or low (0.1%) dose of ingested CPZ with disruption of the blood brain barrier (BBB), using pertussis toxin (PT), was assessed in mice. 0.2% CPZ(±PT) for 5 weeks produced oligodendrocytosis, demyelination and gliosis plus marked splenic atrophy (37%) and reduced levels of CD4 (44%) and CD8 (61%). Conversely, 0.1% CPZ(±PT) produced a similar oligodendrocytosis, demyelination and gliosis but a smaller reduction in splenic CD4 (11%) and CD8 (14%) levels and no splenic atrophy. Long-term feeding of 0.1% CPZ(±PT) for 12 weeks produced similar reductions in CD4 (27%) and CD8 (43%), as well as splenic atrophy (33%), as seen with 0.2% CPZ(±PT) for 5 weeks. Collectively, these results suggest that 0.1% CPZ for 5 weeks may be a more promising model to study the ‘inside-out’ theory of Multiple Sclerosis (MS). However, neither CD4 nor CD8 were detected in the brain in CPZ±PT groups, indicating that CPZ-mediated suppression of peripheral immune organs is a major impediment to studying the ‘inside-out’ role of the adaptive immune system in this model over long time periods. Notably, CPZ(±PT)-feeding induced changes in the brain proteome related to the suppression of immune function, cellular metabolism, synaptic function and cellular structure/organization, indicating that demyelinating conditions, such as MS, can be initiated in the absence of adaptive immune system involvement.

scholarly journals Does Resetting the Immune System Fix Multiple Sclerosis?

2019 ◽  
Vol 47 (1) ◽  
pp. 1-10
Author(s):  
Gauruv Bose ◽  
Simon D. X. Thebault ◽  
Harold L. Atkins ◽  
Mark S. Freedman
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Therapeutic Option ◽  
Disease Course ◽  
Phase Ii Trials ◽  
Durable Response ◽  
Treatment Protocols ◽  
Hematopoietic Stem ◽  
Aggressive Disease ◽  
Conditioning Regimens

Abstract:Multiple sclerosis is the leading non-traumatic cause of disability in young adults, affecting up to 100,000 Canadians. This chronic inflammatory and neurodegenerative disease of the central nervous system leads to irreversible neurologic disability if inadequately controlled. Though many current medications are available that reduce inflammatory damage, most patients continue to show some evidence of disease activity and accrue disability. In this review, we discuss the role of immune ablation followed by autologous hematopoietic stem cell transplantation (AHSCT), a therapeutic option for select patients with a more aggressive disease course. By “resetting” the immune system with a variety of ablative conditioning regimens, followed by immune reconstitution, this therapy has shown a durable response in halting evidence of inflammatory activity in most patients, without the need for continued disease-modifying therapies (DMT). Since the introduction of this therapy, there have been advances in patient selection and supportive care, such that morbidity has significantly declined and treatment-related mortality is minimized. Recent phase-II trials have shown excellent results in efficacy and safety of AHSCT; however, challenges exist which require ongoing study. The future challenges include comparing the variety of AHSCT conditioning regimens with each other as well as with existing highly effective DMT; identifying patients with an aggressive disease course through novel biomarkers who may benefit the most from AHSCT; and surveillance of long-term outcomes of different treatment protocols. In select patients, replacing the immune system with AHSCT holds promise of fundamentally altering the trajectory of their aggressive disease course.

scholarly journals COVID-19 and Cytokine Storm

2020 ◽  
Author(s):  
Mustafa Kurtuluş ◽  
İbrahim Pirim
Keyword(s):  
Immune Response ◽  
Host Response ◽  
Distress Syndrome ◽  
Multiple Organ ◽  
Past Century ◽  
Viral Agent ◽  
Disease Course ◽  
Cytokine Storm ◽  
The Past ◽  
Novel Coronavirus

Although the etiopathogenesis of infections has been largely illuminated by technical and scientific developments in the past century; many issues are still not clear today. The word “there is no disease, there is a patient” is stil valid today. Because the immune response of the host is as important as the virulence of the pathogen in infections and disease course can vary a lot according to the person. Cytokine Storm is seen exactly in a group of diseases where the host response is very prominent. For this reason, Cytokine Storm Syndrome (CSS) is mostly mentioned. CSS emerging due to different inflammatory etiologies; it is an overwhelming systemic inflammation, hemodynamic imbalance, multiple organ failure, and potentially leading to death. After being first seen in Influenza in 2003 as a viral agent, CSS was seen in SARS-Cov, MERS-CoV and SARS-CoV2, which were found to be the las thuman disease from the Corona viridea family.The novel coronavirus SARS-CoV2 causes COVID-19, a pandemic threatening millions. Uncontrolled production of pro-inflammatory mediators contributes to, acut respiratory distress syndrome (ARDS) and cytokine storm syndrome in COVID-19.

scholarly journals TrackSOM: mapping immune response dynamics through sequential clustering of time- and disease-course single-cell cytometry data

2021 ◽  
Author(s):  
Givanna Haryono Putri ◽  
Jonathan Chung ◽  
Davis N Edwards ◽  
Felix Marsh-Wakefield ◽  
Suat Dervish ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
West Nile Virus ◽  
Immune Cells ◽  
Immune Cell ◽  
West Nile Virus Infection ◽  
Cell Populations ◽  
Disease Course ◽  
Response Dynamics ◽  
Over Time

Mapping the dynamics of immune cell populations over time or disease-course is key to understanding immunopathogenesis and devising putative interventions. We present TrackSOM, an algorithm which delineates cellular populations and tracks their development over a time- or disease-course of cytometry datasets. We demonstrate TrackSOM-enabled elucidation of the immune response to West Nile Virus infection in mice, uncovering heterogeneous sub-populations of immune cells and relating their functional evolution to disease severity. TrackSOM is easy to use, encompasses few parameters, is quick to execute, and enables an integrative and dynamic overview of the immune system kinetics that underlie disease progression and/or resolution.

scholarly journals Steroid harms if given early in COVID-19 viraemia

2021 ◽  
Vol 14 (2) ◽  
pp. e241105
Author(s):  
Kanupriya Arora ◽  
Prasan Kumar Panda
Keyword(s):  
Immune Response ◽  
Immune Regulation ◽  
Severe Disease ◽  
Preventive Measure ◽  
Disease Course ◽  
Supportive Treatment ◽  
Cytokine Storm ◽  
Adaptive Immune ◽  
The One ◽  
Anti Inflammation

COVID-19 is a biphasic illness with an initial viraemia phase and later effective adaptive immune phase, except in a minority of people who develop severe disease. Immune regulation is the key target to treat COVID illness. In anticipation, an elderly man self-medicated himself with dexamethasone on the day of symptom onset of a flu-like illness, took other symptomatic measures and was tested positive for SARS-CoV-2. His condition deteriorated with each passing day resulting in hospitalisation. He demanded oxygen and declared as severe COVID. With supportive treatment, he recovered after the 20th day of illness. Immunosuppression and anti-inflammation are likely to benefit when the immune response is dysregulated and turning into a cytokine storm. A medication that has saved many could be the one predisposing to severity if taken as a preventive measure, too early in the disease course, especially the viraemia phase.

scholarly journals Cytokine Storm: The Primary Determinant for the Pathophysiological Evolution of COVID-19 Deterioration

2021 ◽  
Vol 12 ◽  
Author(s):  
Ruirong Chen ◽  
Zhien Lan ◽  
Jujian Ye ◽  
Limin Pang ◽  
Yi Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
Acute Respiratory Distress Syndrome ◽  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Distress Syndrome ◽  
The Novel ◽  
Cytokine Storm ◽  
Major Threat ◽  
Primary Determinant ◽  
Multi Organ Dysfunction Syndrome

The coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing major threat to global health and has posed significant challenges for the treatment of severely ill COVID-19 patients. Several studies have reported that cytokine storms are an important cause of disease deterioration and death in COVID-19 patients. Consequently, it is important to understand the specific pathophysiological processes underlying how cytokine storms promote the deterioration of COVID-19. Here, we outline the pathophysiological processes through which cytokine storms contribute to the deterioration of SARS-CoV-2 infection and describe the interaction between SARS-CoV-2 and the immune system, as well as the pathophysiology of immune response dysfunction that leads to acute respiratory distress syndrome (ARDS), multi-organ dysfunction syndrome (MODS), and coagulation impairment. Treatments based on inhibiting cytokine storm-induced deterioration and occurrence are also described.

scholarly journals Vaccine or Life: Can We Turn the Ongoing Pandemic Into a Useful Experience?

2021 ◽  
pp. 1-3
Keyword(s):  
Immune Response ◽  
Public Opinion ◽  
Immune System ◽  
Medical Center ◽  
Cytokine Storm ◽  
Medical Field ◽  
Fundamental Research

Fundamental research, except for the medical field, is set behind by the continuing pandemic. Three main directions are shaping up in the scientists’ effort to defeat the COVID-19 virus: (i) immunization by vaccine, (ii) healing infected patients with specific medicines, or (iii) prevention of extreme symptoms via strengthening the person’s immune system, while avoiding the cytokine storm. Public opinion focused on which vaccine may be better, how long it would protect its recipient and, most importantly, when does it become available to the residents of a certain country? Does coronavirus treatment with EXO-CD24 show real promise? Under development at Tel Aviv’s Ichilov Medical Center, EXO-CD24 has been demonstrated to moderate immune response, and to help preventing cytokine storm…

scholarly journals Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 565
Author(s):  
Ali A. Rabaan ◽  
Shamsah H. Al-Ahmed ◽  
Mohammed A. Garout ◽  
Ayman M. Al-Qaaneh ◽  
Anupam A Sule ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Viral Entry ◽  
Inflammatory Responses ◽  
Organ Damage ◽  
Multiple Organ ◽  
Special Focus ◽  
Cytokine Storm ◽  
Damage Recognition ◽  
Gender And Age

The pathogenesis of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still not fully unraveled. Though preventive vaccines and treatment methods are out on the market, a specific cure for the disease has not been discovered. Recent investigations and research studies primarily focus on the immunopathology of the disease. A healthy immune system responds immediately after viral entry, causing immediate viral annihilation and recovery. However, an impaired immune system causes extensive systemic damage due to an unregulated immune response characterized by the hypersecretion of chemokines and cytokines. The elevated levels of cytokine or hypercytokinemia leads to acute respiratory distress syndrome (ARDS) along with multiple organ damage. Moreover, the immune response against SARS-CoV-2 has been linked with race, gender, and age; hence, this viral infection’s outcome differs among the patients. Many therapeutic strategies focusing on immunomodulation have been tested out to assuage the cytokine storm in patients with severe COVID-19. A thorough understanding of the diverse signaling pathways triggered by the SARS-CoV-2 virus is essential before contemplating relief measures. This present review explains the interrelationships of hyperinflammatory response or cytokine storm with organ damage and the disease severity. Furthermore, we have thrown light on the diverse mechanisms and risk factors that influence pathogenesis and the molecular pathways that lead to severe SARS-CoV-2 infection and multiple organ damage. Recognition of altered pathways of a dysregulated immune system can be a loophole to identify potential target markers. Identifying biomarkers in the dysregulated pathway can aid in better clinical management for patients with severe COVID-19 disease. A special focus has also been given to potent inhibitors of proinflammatory cytokines, immunomodulatory and immunotherapeutic options to ameliorate cytokine storm and inflammatory responses in patients affected with COVID-19.

scholarly journals Cytokine Storm: A Suicidal Immune Response to Novel Corona Virus

2021 ◽  
pp. 31-37
Author(s):  
Jignakumari J. Gohil ◽  
Chiragkumar J. Gohil
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Mortality Rate ◽  
Respiratory Tract ◽  
Inflammatory Reaction ◽  
Lung Damage ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Life Saving ◽  
Host Killing

SARS-CoV-2 virus is responsible for the COVID-19 disease in patients. Only 15-20 % of COVID-19 patients have developed severe pulmonary symptoms and illness, which are fatal to patients. Hyper-immune response to the SARS-CoV-2 virus by the host’s immune system causes the release and over production of certain kinds of inflammatory mediators and cytokines. And it results in the cytokine storm. Cytokine storm produces the hyper inflammatory reaction, which deteriorates the cells and tissue. This type of immune response is host killing and suicidal response to the SARS-CoV-2 virus by the host. This suicidal response ultimately leads to lung damage, respiratory tract pneumonia, ARDS, multi-organ failure at a later stage and ultimately death. Hence, it needs to suppress the hyper-functioning of the immune system to inhibit the cytokine release and cytokine storm. Anti-inflammatory and immuno-modulatory drugs can be repurposed to manage the cytokine storm and hyper-immune response. Inhibition and management of the host’s suicidal immune response and cytokine storm, could be life-saving and reduce the mortality rate in COVID-19 patients.

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