Cytokines

Cytokines are the primary intercellular chemical messengers of the immune system. Chemically, they are water-soluble proteins and glycoproteins with a mass of 8 to 30 kDaltons (kDa). These protein messengers are produced and released by cells of the immune system such as B-lymphocytes, macrophages and T-lymphocytes. Their actions are essential to the the activation and control of immune responses and the development of blood cells. Once they attach to the surface of a target cell, they may invoke a second messenger system, which causes a release, inside the cell, of chemical messenger(s) that cause specific activities. Those activities may include the extracellular release of additional, usually differentiated cytokines, so cells amplify cytokines.

In biology, cytokines are "non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner." Examples include growth factors,interferons, interleukins, and tumor necrosis factor.

Cytokine is not the universal name for the group. Other name refer to sources of specific kinds of cytokines, or their categorizing by target of action.

Once the amino acid sequence of a cytokine is known, by convention, it is reclassified as an interleukin.

Categorizing by source

They may be named by their source:

• lymphokine (cytokines made by lymphocytes)
• monokine (cytokines made by monocytes)
• chemokine (cytokines with chemotactic activities)
• interleukin (cytokines made by one leukocyte and acting on other leukocytes).

Categorizing by target

They also may be categorized by their target; some cytokines have more than one of the type:

• On the secreting cell: autocrine cytokine
• on nearby cells: paracrine
• on distant cells: endocrine action. This last group overlaps releasing factors and hormones.

Categorizing by structure

Structurally, cytokines can be classified into several classes:

• four alpha-helix bundle family consisting of the IL-2 subfamily (including erythropoietin and thrombopoietin,
• interferon subfamily (approximately 20 α-interferon and 1 β-interferon in Type I, one β-interferon in Type II) and the IL-10 subfamily
• IL-1 family (primarily IL-1 and IL-18)
• IL-17 family
• chemokine family

Categorizing by receptor

• Immunoglobulin (Ig-x) superfamily are found throughout the body (eg, IL-1 receptor types)
• Interferon (type 2) family includes IFN beta and gamma receptors.
• Tumor necrosis factor (TNF) (type 3) family is composed of receptors sharing a cystein-rich extracellular binding domain and includes non-cytokine ligands such as CD40, CD27, and CD30 in addition to TNF.
• 7-transmembrane helix family that includes all G-protein coupled receptors (GPCRs), such as the chemokine receptors CXCR4 and CCR5 (HIV binding proteins) belong to this family.

Categorizing by hybrid, functional organization

Major chemical families include:

• Interleukins (IL) (formally called lymphocyte activating factor)
• Interferons (INF)
• Tumor necrosis factors (TNF)
• Granulocyte-Monocyte Colony Stimulating Factor
• Erythrocyte Stimulating Factor
• Macrophage chemotactic protein (MCP)
• Macrophage inflammatory protein (MIP)

Selected cytokines

Name(s)	Source	Target	Function
Il-1a, IL-1b	monocytes, macrophages, B-lymphocytes, DC	Th cells, B cells, NK cells, general inflammation-susceptible	Th cell co-stimulation, B-lymphocyte maturation and proliferation, NK cell activation, general inflammation
IL-2	Th1 cells	activated T- and B-lymphocytes, NK cells	growth, proliferation, activation
IL-3	Th cells, NK cells	stem cells, mast cells	stem cell growth and differentiation, mast cells growth and histamine release
IL-4	Th2 cells	activated B cells, macrophages, T cells	IgG1 and IgE synthesis ,macrophage MHC Class II, T cell growth, B cell growth
IL-5	Th2 cells	activated B cells	proliferation and differentiation, IgA synthesis
IL-6	monocytes, macrophages, T-helper subtype 2 lymphocytes (Th2 cells), stromal cells	activated B cells, plasma cells, stem cells,	differentiate B lymphocytes (B cells) into plasma cells, plasma cell antibody secretion, stem cell differentiation, general acute phase response
IL-7	marrow and thymus stroma	stem cells	differentiation
IL-8	macrophages and endothelial cells	neutrophils	chemotaxic attraction of neutrophils
IL-10	Th2 cells	macrophages, B-cells	downregulate cytokine production by macrophages, activate B-lymphocytes
IL-12	macrophages, B cells	activated Tc cells, natural killer cells	In combination with IL-2, differentiate Tc cells into CTL; activate NK
IL-13	TH2 cells		Similar to IL-4
GM-CSF	Th cells	progenitor cells	growth and differentiation of monocytes and dendritic cells (DC)