Multiple Sclerosis is a neurological, immune-mediated disorder Multiple Sclerosis is a neurological, immune-mediated disorder. What causes it? Environmental Factors Genetics Viruses Immunologic Factors

The Role of Cytokines in the Progression of Multiple Sclerosis, and Therapeutic Applications     Sanketh Andhavarapu G/T Independent Research Mount Hebron High School Dr. Kiehl, Advisor   

Overview: Background Research Question and Hypothesis My Research- Synthesis Paper Data Collection Final Product Overview:

What is Multiple Sclerosis? Neuro-inflammatory disease 2.5 million cases worldwide Causes are unknown Progression is unpredictable Affects women twice as much than men Typically affects ages 20-40 http://health.howstuffworks.com/diseases-conditions/musculoskeletal/multiple-sclerosis1.htm

What are Cytokines? Small Secreted Proteins that aid in: Immune responses Cell Signaling

Cytokines in Neuroinflammatory Diseases Pro-inflammatory cytokines Involved in the upregulation of inflammatory actions Anti-inflammatory cytokines Regulate the proinflammatory cytokine response http://www.quantumday.com/2012/07/drug-controls-brain-inflammation-to.html

How are proinflammatory and anti-inflammatory cytokines involved in the pathogenesis of multiple sclerosis, and how can this relationship be used in treatments to ameliorate the symptoms? My Research Question

Cytokines play an immense role in multiple sclerosis; suppressing proinflammatory cytokines and inducing anti-inflammatory cytokines will potentially slow down the progression of the disease and ameliorate inflammation, relapse rate, and exacerbations. Hypothesis

The Innate and Adaptive Response Innate Response The immediate and initial immune response Leads to the adaptive response Adaptive Response Initiated by the presentation of a specific antigen to T lymphocytes by antigen presenting cells Activates several types of T-cells http://classes.midlandstech.edu/carterp/Courses/bio211/chap21/Slide1.JPG

T-cells Cytotoxic T cells Regulatory T cells Helper T cells Destroy virus infected cells Regulatory T cells Dampen the immune response Helper T cells Recognizes foreign substances Activates other T cells Th1, Th2, Th17 subtypes are proliferated in Multiple Sclerosis

How are T-cells related to cytokines?

Cytokine Levels in Multiple Sclerosis The balance between proinflammatory and anti-inflammatory cytokines is lost in different stages of MS Proinflammatory cytokines are upregulated Anti-inflammatory cytokines are also upregulated Increased proinflammatory cytokine levels are a result of the activated T cells Anti-inflammatory cytokine level increases in an attempt to control the proinflammatory response

https://academic. oup. com/ajcp/article-lookup/doi/10 https://academic.oup.com/ajcp/article-lookup/doi/10.1309/AJCP7UBK8IBVMVNR

Examples of Cytokines Proinflammatory: Anti-inflammatory: Interferon-gamma Tumor Necrosis Factor- alpha Interleukin- 1 beta Interleukin- 12 Interleukin- 17 Anti-inflammatory: Interleukin-1 receptor antagonist Interleukin-4 Interleukin-6 Interleukin-10 Interleukin-11 Interleukin-13 https://www.researchgate.net/figure/7833977_fig3_FIG-3-Fluorescent-double-staining-for-cytokines-and-CD68-in-skin-biopsies-from-patients

Current Work- Data Collection Meta- Analysis 4 scholarly articles Focusing on how effective treatments target cytokines Similarities in mechanisms of action Glatiramer Acetate (Copaxone) Interferon-beta (Betaseron)

The Articles I Chose Randomized Study Combining Interferon & Glatiramer Acetate in Multiple Sclerosis Multiple sclerosis is associated with an imbalance between tumor necrosis factor-alpha (TNFa)- and IL-10-secreting blood cells that is corrected by interferon-beta (IFNb) treatment Regulatory effects of IFN-b on production of osteopontin and IL-17 by CD4+ T Cells in MS Mechanism of action of glatiramer acetate in multiple sclerosis and its potential for the development of new applications

My Findings Both GA and IFN-b upregulated anti-inflammatory cytokine populations and downregulated proinflammatory cytokine populations during relapse. Balance between cytokines was restored after treatment.

Final Product Journal Article Submitting to National High School Journal of Science Present to researchers and interns studying multiple sclerosis in a research laboratory. Present to interested High School students

QUESTIONS?