Cytokine Network

Cytokines are a category of signaling molecules that mediate and regulate immunity, inflammation, hematopoiesis, and many other cellular processes, forming a cytokine network. Cytokines were initially identified as products of immune cells that act as mediators and regulators of immune processes but many cytokines are now known to be produced by cells other than immune cells and they can have effects on non-immune cells as well. Cytokines can also be secreted by glial cells of the nervous system. Cytokine is a general name; other names are defined based on their presumed function, cell of secretion, or target of action. For example, cytokines made by lymphocytes can also be referred to as lymphokines, while interleukins are made by one leukocyte and act on other leukocytes. And chemokines are cytokines with chemotactic activities. Cytokines may act on the cells that secrete them (autocrine action), on nearby cells (paracrine action), or in some instances on distant cells (endocrine action).

Cytokines that play a major role in the innate immune system include: TNF-α, IL-1, IL-10, IL-12, IFN-α, IFN-β, IFN-γ, and chemokines. TNF alpha produced by activated macrophages is response to microbes, especially the lipopolysaccharide (LPS) of Gram negative bacteria. It is an important mediator of acute inflammation. It mediates the recruitment of macrophages and neutrophils to sites of infection by stimulating endothelial cells to produce adhesion molecules and by producing chemotactic cytokines - chemokines. TNF- α also acts on the hypothalamus to produce fever and it promotes the production of acute phase proteins. Interleukin 1 is another inflammatory cytokine produced by activated macrophages. It promotes activation, costimulation, and secretion of cytokines and other acute-phase proteins. Interleukin 10 is produced by activated macrophages, B cells, and T helper cells. It is predominantly an inhibitory cytokine. Interleukin 10 decreases antigen presentation and the expression of class II MHC and co-stimulatory molecules on macrophages, resulting in a dampening of immune responses. Interleukin 12 is produced by activated macrophages, B cells and dendritic cells. It induces the differentiation of Th cells to become Th1 cells and enhances the cytolytic functions of T cytotoxic cells and NK cells. Interferon-alpha and interferon-beta are cytokines produced by macrophages, dendritic cells, and many other cell types. They promote resistance to viral pathogens and promote increased expression of MHC class I. Interferon gamma is an important cytokine produced primarily by Th1 cells, and also by NK cells in a lesser extent. It promotes activation of APCs and cell-mediated immunity, and increase expression of MHC class II molecules. IFN gamma has numerous functions in both innate immune and adaptive immune systems. Chemokines are chemotactic cytokines produced by many kinds of leukocytes and other cell types. They represent a large family of molecules that function to recruit leukocytes to sites of infection and play a role in lymphocyte trafficking.

Another group of cytokines that play a critical role in adaptive immune system include IL-2, IL-4, IL-5, TGF-β, IL-10 and IFN-γ. Interleukin 2 is a type I cytokine produced primarily by T helper cells. It is the major growth factor for T cells. It also promotes the growth of B cells and can activate NK cells and monocytes. Interleukin 4 is produced by T cells and mast cells. It stimulates proliferation and differentiation of Th2 cells, while inhibit Th17 development. Interleukin 4 also stimulates Ig class switching to the IgE isotype. Interleukin 5 is a cytokine produced by Th2 cells. It functions to promote the growth and differentiation of B cells and eosinophiles. Transforming growth factor beta is a cytokine and also is a growth factor produced by T cell, macrophages, and many other cell types. It is primarily an inhibitory cytokine, which inhibits the proliferation of T cells and blocks the effects of pro-inflammatory cytokines.