Cytokines: Chemical Mediators in the Immune System

       

 

1.            Cytokines are hormonelike chemical messengers secreted by lymphocytes and macrophages that affect the immune response.

 

 

2.            Mediators affecting Lymphocytes

 

Cytokine

Major Source

Important Functions

Interleukin-1

Macrophages

Stimulates growth of lymphocytes, neutrophils, epithelial cells and fibroblasts.

Stimulates helper T cells to differentiate and produce IL-2.

Endogenous pyrogen: acts on hypothalamus to cause fever.

Inflammation mediator.

Interleukin-2

TH1 cells

Stimulates growth of both helper and cytotoxic T cells.

Acts synergistically with IL-4 to stimulate growth of B cells.

Interleukin-4

TH2 cells

Stimulates B cell growth.

Increase isotype switching and IgE synthesis.

Increase number of TH2 cells.

Interleukin-5

TH2 cells

Stimulates B cell differentiation.

Enhances synthesis of IgA.

Stimulates the production and activation of eosinophils.

Interleukin-6

Helper T cells

Stimulate B cell differentiation.

Interleukin-10

TH2 cells

Inhibits development of TH1 cells by limiting interferon-g production.

Interleukin-12

Macrophages

Promotes development of TH1 cells by stimulating interferon-g production.

 

 

3.            Mediators affecting Macrophages and Monocytes

 

 

Cytokine

Major Source

Important Functions

Chemotactic factors: C5a, IL-8

Released during inflammation

Attracts monocytes and macrophages to site of tissue injury and infection.

Interferon-g

TH1 cells

Stimulates phagocytosis and killing by macrophages.

Increases class I and II MHC expression.

 

 

4.            Mediators affecting Polymorphonuclear Leukocytes

 

 

Cytokine

Major Source

Important Functions

Chemotactic factors: C5a, IL-8

Released during inflammation

Attracts neutrophils, basophils, and eosinophils selectively to the site of injury and inflammation.

TNF-a

Macrophages

Low concentration: activates neutrophils and increases their adhesion to endothelial cells.

 

 

5.            Mediators affecting Stem cells

 

 

Cytokine

Major Source

Important Functions

IL-3

Helper T cells

Supports the growth and differentiation of bone marrow stem cells.

GM-CSF

T lymphocytes

Macrophages

Stimulates the growth of granulocytes and macrophages.

Enhances the antimicrobial activity of macrophages.

Used clinically to improve regeneration of these cells after bone marrow transplantation.

G-CSF

Macrophages

Fibroblasts

Endothelial cells

Enhances the development of neutrophils from stem cells.

Used clinically to prevent infection in patents who have received cancer chemotherapy.

 

 

6.            Mediators with Other effects

 

 

Cytokine

Major Source

Important Functions

Interferon-a

Leukocytes

Generates antiviral and antiproliferative actions.

Interferon-b

Fibroblasts

Generates antiviral and antiproliferative actions.

TNF-a

Macrophages

High concentrations: important mediator of endotoxin-induced septic shock.

Cachectin: inhibits lipoprotein lipase in adipose tissue, reducing the utilization of fatty acids.

Causes death and necrosis of certain tumors.

TNF-b

T lymphocytes

Stimulates B cell proliferation.

Generates antiparasitic action (malaria, trypanosomiasis).

Mediates inflammatory reactions in endotoxic shock.

Nitric oxide

Macrophages

Vasodilation

 

 

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