AMI 1031 Cytokine 420 x 594

The cytokine network

cellular communication assays
Biotrak : Assay solutions for disease research ™

Inflammation Hematopoiesis
EPO EPO
FEVER
SCF
IL-1α, IL-1β, TNFα, IL-6, LIF, IL-11, OSM, BRAIN IL-9

1
TNFβ CNTF, CT-1

L-
▼ ▼ ERYTHROBLAST

,I
HYPOTHALAMUS IL-4 RED CELLS

SF
Type I acute phase Type II acute phase
proteins: proteins:

-C
IL-6
Myeloid

M
SAA, serum amyloid A fibrinogen TNF PGE2 G
CRP, C-reactive protein haptoglobin (human) Progenitor
complement C3 α1-antichymotrypsin
IL-1
- 3,
haptoglobin (rat) α1-antitrypsin IL IL-5
α1-acid glycoprotein α2-macroglobulin (rat) CFU-GM
CRF
ACTH
Hematopoietic PMN BASOPHIL
ACUTE Stem Cell IL-6 IL-11
PHASE Tpo
PROTEINS

ACTH
IL-3 G-CSF
IL-7
M-CSF PMN EOSINOPHIL
HEPATOCYTES

LIVER IL-6
LIF
IL-1
Lymphoid
MEGAKARYOCYTE
TNF PMN NEUTROPHIL
IL-1 IL-6 Progenitor Tpo MONOCYTE

KIDNEY
CORTICOSTEROIDS PLATELETS
MACROPHAGE

IL-1
IUM

1
EL

IFNγ

The chemokine family

ITH
EP

TNFα 1 Proinflammatory cytokines are

IL-6
2 released by damaged or infected Chemokine Size Characteristics Family
tissue RANTES 68aa
MIP-1α, MIP-1β (macrophage inflammatory proteins) 70aa, 69aa
2 Adhesion molecule expression TCA3 (T cell activation gene 3) 69aa
LP ERIA

(selectin family) allows leucocytes I-309 (human counterpart of the murine TCA3?) 74aa
Generally chemoattractant for monocytes; C-C Chemokines
and endothelial cells to bind. memory CD4+ lymphocytes, and
MCP-1 (monocyte chemotactic protein-1), MCP-2, MCP-3 76aa
3
S

eosinophils, with variable selectivity.

CT

The leucocyte slows and rolls MCP-4 75aa NOT for neutrophils.
D

along the endothelium

BA
UN

C-C and Eotaxin, Eotaxin 2 74aa, 78aa

WO

C-X-C 3 Chemokine release (C-C and MPIF, MPIF-2 (myeloid progenitor inhibitory factor) 99aa, 93aa
Chemokines PF4 (platelet factor 4) 70aa
C-X-C) causes integrin activation.
4 This permits firm binding with the PBP (platelet basic protein) and proteolytic derivatives 96aa
Platelet chemokines
βTG (Beta thromboglobulin), CTAPIII 83aa (βTG – form V)
integrin ligands ICAM and VCAM (connective tissue activating peptide III), NAP-2 81aa (βTG – form VI)
Generally chemoattractant for neutrophils C-X-C Chemokines
4 Leucocytes flatten on the IL-8/NAP-1/GCP (interleukin 8/neutrophil 77aa (IL-8) and lymphocytes, NOT for monocytes
0 flow activating protein 1/granulocyte chemotactic protein)
endothelial cell surface and (with the exception of PF4).
IP-10 (IFN-γ inducible protein 10) 77aa
then extravasate through the
ENA78 (epithelial-derived neutrophil attractant-78) 78aa Non-platelet
endothelium to the tissue to chemokines
mig (monokine induced by IFN-γ) 103aa
combat damage
GCP-2 (granulocyte chemotactic protein-2) 70aa, 73aa, 75aa forms
MGSA (melanocyte growth stimulatory activity)/gro proteins 73aa
Chemotactic activity for lymphocytes,
Lymphotactin 93aa C Chemokine
NOT for monocytes or neutrophils.

Immune response The cytokine family

Cytokine Molecular Form Functions
EPO, Erythropoietin 166aa synthesized by peritubular kidney cells, induces differentiation of late determined and differentiated progenitor
cells of erythropoiesis and regulates the proliferation of erythropoietic progenitor cells.
MACROPHAGE/MONOCYTE ANTIGEN
Fas Ligand (FasL) monomer 278aa type II trans-membrane protein of the TNF family which mediates apoptotic effects through its receptor Fas.
AND DENDRITIC CELLS ENDOCYTOSE FasL is also active as a soluble protein, as a product of cleavage by metalloproteases.
G-CSF, Granulocyte colony enhances the differentiation and activation of neutrophils, stimulates the production of neutrophil
stimulating factor monomer 174aa and macrophage colonies in vitro
GM-CSF, Granuloctye macrophage promotes the growth and differentiation of multipotential progenitor cells, stimulates all cells in the
MHC II colony stimulating factor monomer 127aa granulocyte, macrophage, and eosinophil lineage
MHC I
monomer; many species
α /ββ, Interferon α /ββ
IFNα (90% homologous) have been anti-viral activity stimulates macrophage activity, modulates MHC class I and class II protein expression
identified 166/165aa; β, 166aa on various cell types, regulates the development of specific immune responses

anti-viral activity stimulates macrophage activity, modulates MHC class I and class II protein expression
IFNγγ, Interferon-γγ homodimer 143aa on various cell types, regulates the development of specific immune responses
monomer 159aa, also biologically produces a wide variety of effects on the differentiation and function of cells involved in inflammatory and
α, Interleukin-1α
IL-1α α
ANTIGEN ANTIGEN active membrane bound precursor form immune responses; also affects the CNS and endocrine system
PRESENTING CELL PRESENTING CELL
produces a wide variety of effects on the differentiation and function of cells involved in inflammatory and
IL-1ββ, Interleukin-1ββ monomer 153aa immune responses; also affects the CNS and endocrine system
IL-1ra, Interleukin-1 receptor antagonist monomer 152aa inhibits the biological activity of IL-1 by competing for binding to IL-1 receptors
MHCI MHC II
stimulates T cell proliferation and differentiation, enhances cytolytic activity of NK cells and production
TCR IL-2, Interleukin-2 monomer 133aa
IL-1 TCR of LAK cells, promotes proliferation and Ig secretion of activated B cells
CD3 IL-10
CD3 synergizes with lineage restricted factors to stimulate the production and differentiation of macrophages,
IL-12 IL-3, Interleukin-3 monomer 133aa neutrophils, eosinophils, basophils, mast cells, megakaryocytes and erythroid cells, supports the proliferation
FasL of multi-potential progenitor cells
induces the differentiation of naive CD4 T cells into Th2 like cells, induces the proliferation and
PRECYTOTOXIC T HELPER T IL-4, Interleukin-4 monomer 129aa differentiation of B cells, exhibits diverse effects on T cells, monocytes, granulocytes as well as fibroblasts
IL-2Rβ CD8 CD4 +IL-4 and endothelial cells
stimulates the growth and differentiation of eosinophils, activates eosinophil function, chemotactic
IL-5, Interleukin-5 homodimer 115aa for eosinophils
β
2R activates haematopoietic progenitor cells and shortens their G0 period, induces the maturation of megakaryocytes
IL- IL-2
IL-2 and an increase in platelet number, induces growth and/or differentiation of T cells, B cells, hepatocytes,
IL-2R IL-2R MEMBRANE Ig IL-6, Interleukin-6 monomer 184aa keratinocytes and nerve cells, stimulates the production of acute phase proteins by hepatocytes
2
IL- -12 Th1 Th2 supports the growth of pre-B and pro-B cells, supports the proliferation of T cells, stimulates the proliferation,
LGL +IL CD4 CD4 IL-7, Interleukin-7 monomer 152aa cytotoxic activity and generation of cytotoxic T cells and LAK cells
(NK) B dimer N-terminal variants exhibits chemotactic activity in vitro for neutrophils, T cells and basophils, activates neutrophils to release
Lymphocyte IL-8, Interleukin-8
IL-2R 69, 72, 77 or 79aa lysosomal enzymes, induces adhesion of neutrophils to endothelial cells
Fas IL-4
synergizes with EPO to support the development of erythroid burst forming units by bone-marrow cells,
Cytotoxic IFNγ IL-9, Interleukin-9 monomer 126aa enhances the in vitro survival of T cell lines. Mouse IL-9 has mouse mast cell enhancing activity
Tc
IFN γ IL-10, Interleukin-10 homodimer 160aa
potent immunosuppressant of macrophage functions, suppresses production of pro-inflammatory cytokines
CD8 by activated monocytes/macrophages, enhances B cell proliferation and Ig secretion
FasL IL-4
IL-5 synergizes with IL-3 to increase the size, number and average ploidy value colonies of megakaryocytes,
IL-6 B B IL-11, Interleukin-11 monomer 178aa synergizes with IL-3 and IL-4 to shorten the G0 period of early haematopoietic progenitors, stimulates the
IL-10 Lymphocyte Lymphocyte synthesis of hepatic acute-phase proteins
IL-13
heterodimer of p35 and p40 subunits initiates cell-mediated immunity by inducing the differentiation of Th1 cells from uncommitted T cells,
Tc Tc FasL IL-12, Interleukin-12
(197 and 306aa respectively) stimulates the growth and functional activity of Natural killer and T cells
CD8 CD8
Fas induces B cell growth and differentiation, inhibits inflammatory cytokine production by
IL-13, Interleukin-13 (P-600) monomer 132aa monocytes/macrophages
GRANULE TCR TCR
EXOCYTOSIS 483aa produced by CD4+ and CD8+ T cells, follicular dendritic cells and fibroblasts, induces proliferation
IL-14, Interleukin-14
53kDa of activated B cells.
MHCI IL-4 IL-15, Interleukin-15 monomer 468aa induces the proliferation of activated B cells but not resting B cells, inhibits Ig secretion of mitogen-stimulated B cells
FasL IL-13 B B IL-16, Interleukin-16 130aa; 14 kDa lymphocyte chemoattractant factor (LCF) produced by CD8+ T cells in response to: antigen,
Lymphocyte Lymphocyte Active as a 50-60 kDa homotetramer mitogen, histamine and serotonin, chemoattractant for CD4+ T cells and eosinophils
IgE IL-17, Interleukin-17 150aa produced by CD4+ T cells activated by PMA or CD3, induces production of IL-6, IL-8, G-CSF and PGE 2 and
LAK TARGET CELL 15kDa expression of ICAM-1 (from fibroblasts, endothelial and epithelial cells).
SECRETION
KILLING IL-6 IL-18, Interleukin-18 18kDa, 192aa IFNγ Inducing Factor (IGIF), produced by liver cells, induces production of IFNγ by spleen cells, enhances NK cells
cytotoxicity, enhances GM-CSF production and reduces IL-10 production in Con A activated PBMC.
SECRETED Ig homo- and heterodimers of inhibits growth of many cell types, stimulates formation of ECM, stimulates osteoblasts and inhibits
Fas TGF-ββ , Transforming growth factor-ββ three 112aa isoforms osteoclasts; inhibits NK cell activity and T/B cell proliferation with IL-4, stimulates IgA secretion
wide variety of effects due to ability to mediate expression of genes for growth factors and cytokines,
α,
TNF-α trimer 157aa; also
FasL receptors, inflammatory mediators, and acute phase proteins, plays role in host resistance to infection and
α (cachectin)
Tumour necrosis factor-α membrane bound form tumour growth by serving as an immunostimulant and mediator of the inflammatory response
PLASMA CELL TNFββ, Tumour necrosis factor-ββ homotrimer 205aa produced by activated lymphocytes, kills tumour cell lines, increases fibroblast growth, increases expression of MHC
genes and expression of adhesion molecules.
TPO, Thrombopoietin 332aa produced in the liver and kidney, a megakaryocyte colony-stimulating factor and a megakaryocyte maturation factor.

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420 x 594mm
AMI 1031 Cytokine 420 x 594