Cytokines

Cytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted de novo in response to immune stimuli, and usually act briefly, locally, at very low concentrations (the exception being endocrine action at distant cells). Cytokines bind to specific membrane receptors, which then signal the cell via second messengers, often tyrosine kinases, to alter cellular activity (gene expression).

 Complement Receptors  Fc receptors  Immune Cytokines  Immunoglobulins  Interferons  Scavenger Receptors  Toll-like Receptors  Cell Adhesion Molecules  Cell signaling  Receptor Tyrosine Kinases (RTKs)  Receptor Signal Transduction  Second Messengers

Immune Cytokines

Cytokine class Producer cell/tissueTarget cellFunctions

Granulocyte/Monocyte Colony Stimulating Factor (CSF)

G-CSF endothelium, macrophages neutrophil progenitor cells growth and differentiation of neutrophils
GM-CSF Th cells progenitor cells growth and differentiation of monocytes and dendritic cells
M-CSF thymic epithelial cells (TEC), PMN, chondrocytes, glomerular mesangial cells, Ishikawa cells macrophage lineage lymphohematopoietic growth and differentiation of monocytes, enhances expression of differentiation- antigens and stimulates chemotactic, phagocytic, and cytotoxic activities of monocytes

Interleukins

IL-1α, IL-1β pro-inflammatory monocytes macrophages B cells dendritic cells Th cells costimulation
B cells maturation and proliferation
NK cells activation
various inflammation, acute phase response, fever
IL-2 hematopoietin Th1 cells activated T cells and B cells, NK cells cell growth, proliferation, activation, synthesis of antibodies
IL-3 (multi-CSF) hematopoietin Th cells, NK cells stem cells growth and differentiation
mast cells growth, and histamine release
IL-4 hematopoietin Th2 cells activated B cells proliferation and differentiation IgG1 and IgE synthesis
macrophages MHC Class II
T cells proliferation
IL-5 hematopoietin Th2 cells activated B cells proliferation and differentiation IgA synthesis
IL-6 hematopoietin pro-inflammatory IL-6 receptor has two subunits - an alpha subunit that produces ligand specificity, and a p130 receptor subunit. Signals through JAK kinases and activation of Ras-mediated signaling monocytes macrophages Th2 cells stromal cells activated B cells differentiation into plasma cells → secretion of antibodies
T cells costimulator of T cells
stem cells differentiation
various acute phase response
neurons, osteoblasts neuronal differentiation, bone loss

IL-7 hematopoietin

marrow stroma thymus stroma stem cells differentiation into progenitor B and T cells
IL-8 chemokine macrophages endothelial cells neutrophils chemotaxis
IL-10 Th2 cells macrophages inhibition of macrophage function, cytokine production
B cells activation
IL-12 macrophages B cells activated Tc cells differentiation into CTL (with IL-2)
NK cells activation
IL-21 CD4+ T cells B cells, T cells, NK cells

costimulator of T cell proliferation, enhances memory response, and modulates homeostasis

regulator of B cell differentiation to plasma cells, regulator of isotype switching

terminal differentiation of NK cells, enhancing cytotoxic function while also decreasing cellular viability

Interferons  Interferons

IFN-α leukocytes various viral replication MHC I expression
IFN-β fibroblasts various viral replication MHC I expression
IFN-γ Th1 cells, Tc cells, NK cells various viral replication
macrophages MHC expression
activated B cells Ig class switch to IgG2a
Th2 cells proliferation
macrophages pathogen elimination

Macrophage Inflammatory Proteins

MIP-1α chemokine macrophages monocytes, T cells chemotaxis
MIP-1β chemokine lymphocytes monocytes, T cells chemotaxis

Transforming Growth Factor

TGF-β T cells, monocytes monocytes, macrophages chemotaxis
activated macrophages IL-1 synthesis
activated B cells IgA synthesis
various proliferation

Tumor Necrosis Factor

TNF-α pro-inflammatory macrophages, mast cells, NK cells macrophages CAM and cytokine expression
tumor cells cell death
TNF-β lymphotoxin-α (LT) pro-inflammatory Th1 and Tc cells phagocytes B cells phagocytosis, with no production; activation effector cells to infection sites, leukocyte adhesion to endothelial cells, peripheral lymphoid organogenesis, stimulation of B cells
tumor cells cell death through inhibition of tumor angiogenesis

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