Cytokines we should care about

CYTOKINES IN IMMUNE SYSTEM 
  • Basic Introduction
    • Cytokines signal between cells and coordinate the immune response (i.e., they are the hormones of the immune system)
    • They are delivered by cells either to the systemic circulation or to the local environment
    • They bind to high affinity surface receptors
    • Produced by immune cells. But, they are also produced by non immune cells (fibroblasts, endothelial cells)
  • Classification: 4 main designation, but all basically have broad function. 
    • IL
    • Colony-stimulating factors
    • Chemokines
    • Growth Factors
  • Cytokines in normal Immunity
  • Reference:


INTERFERON
  • Virus infected cells release IFN to fight against virus 
  • Helps activate immune cells like Macrophage and NK Cells
  • 3 Types
    • Type I
      • IFN-α, 
      • IFN-β, 
      • IFN-ε, 
      • IFN-κ and 
      • IFN-ω
    • Type II
      •  IFN-γ (gamma): Is the sole member of Type II IFN
    • Type III : IFN-λ (lambda) molecules. Consists of three of these - IFN-λ1, IFN-λ2 and IFN-λ3
TNF-alpha: Amplifies T effector cell response  


How does TNF-alpha act, and can we target its down stream target  CJSAN 2015

TNF-alpha signaling cascade includes JAK pathways. Inhibition of JAK pathway (JAK1, and JAK3 by Tofacitinib led to similar efficacy as Adalimumab in RA. Ofnote, significant side effects (sepsis, neutropenia, elevated Liver enzymes, elevated Cr) were seen as it probably also lacks specificity. 


From Kelly and Firestein's 
IL-6
Source: Monocyte, Fibroblast, T cell, B Cell 
Source: primarily produced by monocytes, fibroblasts and endothelial cells, and by T cells, B cells, keratinocytes and mesangial cells.2 http://dx.doi.org/10.1136/annrheumdis-2016-209668

Function of IL 6:


IL 6 level is increased in RA and PsA but is also noted to be increased in SLE. 
What is the source of IL6 in Lupus?
pDC (monocyte) ? or Fibroblast ? or T cell ? or B Cell 

What is mononulear phagocytes system? It includes Monocyte, Dendritic cells and Marophage. It also include Osteocalsts. 

In vitro, bone marrow precursors and blood monocytes can be stimulated by growth factors23 to generate macrophages (M-CSF or granulocyte-macrophage colony-stimulating factor [GM-CSF]), DCs (GM-CSF, with or without IL-4), or osteoclasts (M-CSF and receptor activator of nuclear factor-κB [NF-κB] [RANK] ligand)

DC are professional APC. 3 major subtypes of DC 
1) pDC 2) conventional DC 3) monocyte derived DC
pDC is specialized to produce high level of INF 

What are Monocytes? 
BM contributes to circulating monocytes. In response to inflammatory stimulation, circulating monocytes gives rise of macrophage, dendritic cells and osteoclast. 


  

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