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/tissue	Target cell	Functions
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