Download Chapter Proposal submission form 1. Provisional title of the

Chapter Proposal submission form
1. Provisional title of the proposed manuscript:
2. Author details
Scientific Title: Professor
Full Name: Selim NALBANT
Affiliation: Medical Faculty of Maltepe University - ISTANBUL / TURKEY
Position: Head of Internal Medicine
3. Co-authors (include all your co-authors if possible at this stage)
3.1.
Scientific Title: Professor
Full Name: Ahmet Merih BİRLİK
Affiliation: Medical School of Dokuz Eylul Universty
Position: Member of Department of Immunology and Rheumatology
4. Keywords (enter min.3): Cytokines, Effector Cells, Rheumatoid Arthritis, anti-cytokine treatment
5. Define your subject area: ‘’Treat to target’’ is the most popular and modern treatment of
today’s medicine for RA. In this concept, target is the cytokines. So, interaction of the cytokines
between every systems of the organism is very important to understand this treatment. We will
draw the repertoire of cytokines with their limits.
6. Write a short description of the chapter, clearly explaining the aims topics research methods
and key results of the chapter.
Introduction: RA is a progressive inflammatory cytokine storming disease which goes by
remissions and flares. In this complex cytokine storm, some articular and systemic effects occur.
The beginning of the all events and the detailed interactions of genetic and environmental factors are
contributory. T cells, B cells and the orchestrated interaction of the cytokines play key roles in the
pathophysiology of RA. Today’s modern rheumatoid arthritis treatment basically targets these
cytokines. While we are doing this, we are basically treat the ‘‘normal and abnormal cytokine
response’’ at the same time. Because we do not know the main reason of this abnormal cytokine
response. So, to manage the RA treatment, understanding the cytokines and the relation between the
effector cells is very important.
The term "cytokine" is derived from a combination of two Greek words - "cyto" meaning
cell and "kinos" meaning movement. Cytokines are cell signaling molecules that are
secreted by immune cells and aid cell to cell communication in immune responses and
stimulate the movement of cells towards sites of inflammation, infection and trauma. So,
the cytokines are the main part of the immune network to provide the communication.
Basically, we may classify cytokines four groups in rheumatoid arthritis pathogenesis:
1-Pro-inflammatory cytokines: IL-1 and TNF-α
2-Over-inflammatory cytokines (cytokine in joints): IL-1, TNF-α, IL-6, IL-15, IL-16, IL-17,
IL-18, IFN- γ, granulocyte macrophage-colony stimulating factor
3- Anti-inflammatory cytokines: IL-4, IL-10, IL-11, and IL-13
4- Natural cytokine antagonists: IL-1 receptor antagonist (IL-1ra), soluble type 2 IL-1 receptor,
soluble TNF receptor (sTNF-RI), and IL-18 binding protein
Body : After the stimulus was occurred, the earliest event in RA pathogenesis is activation
of the innate immune response. In this first step, cytokines plays a role in communication
between the parts of immune system. In second step, antigen-presenting cells present
arthritis-associated antigens to T cells. This step is the starting point of the cytokine storm
which augment the inflammation and stimulate the other systems (such as lipid mediators,
nitric oxide, RANKL-RANK signaling, etc) which cause joint destruction and the organ
involvement.
Conclusion: Differentiation of naı¨ve T cells into Th 17 cells results with synovitis. B cells
further the pathogenic process through antigen presentation and autoantibody and
cytokine production. Joint damage begins at the synovial membrane, where the influx
and/or local activation of mononuclear cells and the formation of new blood vessels cause
synovitis. Pannus, the osteoclast-rich portion of the synovial membrane, destroys bone,
whereas enzymes secreted by synoviocytes and chondrocytes degrade cartilage. The
release of cytokines, especially TNF-a, IL-6 and IL-1, causes synovial inflammation. In
addition to their articular effects, pro-inflammatory cytokines promote the development of
systemic effects, including production of acute-phase proteins, anaemia of chronic disease,
cardiovascular disease and osteoporosis and affect the hypothalamic_pituitary_adrenal
axis, resulting in fatigue and depression. As it was seen, cytokines are the main molecules
at all these stages.