Cytokine

1,Concept

2,Characteristics

3,Classification

4,Biologic activity

5,Cytokine receptor

Mj

Macrophage

IL-1

Activated Th1 cell

a

A

DP56

B

C58

B’

C

NH2COOH

IL-2

Cytockines are low-molecular-weight regulatory proteins or glycoproteins secreted by white blood cells and other cells (vascular endothelial cell, epidermic cell and fibroblast ) in body in response to a

number of stimuli.

1,Concept of cytokine

Engineering cytokines on the market

Cytokine IndicationIFNα Leukemia, hepatitis, cancer, AIDS

IFNγ chronic granuloma, Allergic dermatitis, infectious diseases, rheumatoid arthritis

G-CSF Autograph , hemotocytopenia, AIDS, leukemia , aplastic anemia

GM-CSF

Epo Anemia

IL-2 Cancer, immunodificience, vaccine adjuvant

IFNβ multiple sclerosis

IL-11 thrombocytopenia

SCF Stem cell transplantation combined with G-CSF

EGF Burn, ulcer

bFGF Burn, peripheroneuritis

Autograph , hemotocytopenia, AIDS, leukemia , aplastic anemia

cytokine indication company

IL-10 Dermatitis, infectious diseases, rheumatoid arthritis

Immunex， Schering-Plough

IL-12 Cancer, AIDS GI

Tpo Thrombocytopenia GI，TNF mutant Cancer Many company

Flt3/flk3 Ligand(FL) Cancer Immunex

MPIF-1 Tumor chemotherapy 

HGS

TGF- Chronic ulcer of skin, multiple sclerosis Genzyme

MIP-1 mutant Tumor chemotherapy British Biotech

OPG（ osteoprotegerin）

Osteoporosis Amgen

Mulitkine Tumor CEL-SCI

BlyS Immunodeficiency HGS

Engineering cytokines used in the clinical experiment

(1)Most cytokines are low molecule weight proteins or glycoproteins.

(2)Cytokines come from many kinds of cells----activated immune cells, matrix cells and some tumor cells.

• one cell may secrete many kinds of cytokines,• different cells may secrete the same cytokines.

2,Characteristics

(3)Cytokines act by binding to corresponding receptors on the target cell.

(4)Cytokines act on target cells by the way of paracrine, autocrine or endocrine.

(a) Overview of the induction and function of cytokines. (b) Most cytokines exhibit autocrine and/or paracrine action; fewer exhibit endocrine action.

(5)The biologic effects of cytokines are highly efficient, multiple, overlapped, antagonistic and synergic, which act in a network.

Cytokines can have effect in very low concentration.

One kind of cytokine may have multiple effects.

Several kinds of cytokines may have the same or similar effect.

One kind of cytokine may inhibit activities of other kinds of cytokines.

One kind of cytokine may enhance activities of other kinds of cytokines.

One kind of cytokine may have different targets/activities

3,Classification

(1)Interleukin, IL

(2)Interferon,IFN

(3)Tumor necrosis factor, TNF

(4)Colony stimulating factor, CSF

(5)Chemokine

(6)Growth factor, GF

Based on their functions and structures

IL-13 IL-2

IL-4

(1)Interleukin, IL

The term was used to describe cytokines produced by leukocytes.

In fact, they can be produced by other cell populations. IL-1---IL-35.

Interferon are involved in the defense against viral infection and in activation, modulation of immunity.

Type I interferonIFN-α , IFN-β: Anti-virus and anti-tumor

Type II interferon IFN-γ: Immunoregulation and anti-tumor

(2)Interferon

The anti-virus mechanism of IFN- a

virus

viral replication Inhibition of viral replication

Signal-transduction

IFN-a

IFN-induced proteinstimulating

nuclear nuclear

Tumor necrosis factor (TNF) which can induce tumor necrosis is produced by a variety of cells including activated macrophage and T cell . It has other important biologic effects. TNF-α , TNF-β: Proinflammatory.

(3)Tumor necrosis factor

G-CSFGM-CSF

(4)Colony stimulating factor, CSF

The cytokines that stimulate hemopoietic cells to form cell

colony and participate hemopoietic function are called CSF. For

example, GM-CSF,G-CSF,M-CSF, Epo, Tpo,

The functions of CSF

The cytokines that can promote growthpromote growth of various cells.

Epidermal growth factor， insulin-like growth factor, vascular endothelial growth factor, transforming growth factor.

(5)Growth factor

Vascular endothelial growth factor (VEGF)

VEGF promotes Tumor Angiogenesis

(6)ChemokineChemokines, a group of low-molecular-weight cytokines includin

g interleukin 8, that affect chemotaxisaffect chemotaxis and other aspects of leukoc

yte behavior.

Stromal Derived Factor-1 aSolution Structure Of the Cx3C Chemokine Domain Of Fractalkine

Cytokines possessing chemotaxis

C5a

Cytokine（ IL-8)

(1)Anti-infection and antitumor

(2)Immune regulation

(3)Apoptosis

(4)Stimulating the proliferation and differentiation of hemopoietic stem cells

(5)Promote the growth and differentiation of various cells

(6)Participation and regulation of the inflammatory responses

4,Biologic activity

5,Cytokine receptor

Membrane-binding cytokine receptors.

The receptor consists of extracellular region, transmembrane region and cytoplasmic region.

Grouped by structure:(1) Immunoglobulin family(2) Type I cytokine receptor family(3) Type II cytokine receptor family(4) TNF receptor superfamily(5) Chemokine receptor family

Cytokine receptors

Loss of leads to SCIDSCID： Severe combined immunodeficiency

Some cytokines use a common chain for signal transduction

Leukocyte differentiation antigens and adhesion

molecules

1,Leukocyte differentiation antigens

2,Cluster of differentiation

3,Cell adhesion molecules

1,Leukocyte differentiation antigens

Concept

Leukocyte differentiation antigens are cell surface molecules that may appear or disappear from cell membrane when stem cell differentiate into different lineage cells or when blood cells are in maturation stages and activation status.

2,Cluster of differentiation

Concept

Cluster of differentiation designation is assigned to leukocyte cell surface molecules which are identified by a given group of monoclonal antibodies.

3,Cell adhesion molecules

Concept Concept

The molecules that mediate contact and binding between cells or between cell and extracellular matrix are called cell adhesion molecules (CAM).

1,Master concepts of Cytokine, CD, CAM

2,Be familiar with main properties of cytokines

3,Master the classification of cytokines

Learning Objectives