cytokine(redirected from antitumour necrosis factor (anti-TNF))
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Any of a group of soluble proteins that are released by a cell to send messages which are delivered to the same cell (autocrine), an adjacent cell (paracrine), or a distant cell (endocrine). The cytokine binds to a specific receptor and causes a change in function or in development (differentiation) of the target cell. Cytokines are involved in reproduction, growth and development, normal homeostatic regulation, response to injury and repair, blood clotting, and host resistance (immunity and tolerance). Unlike cells of the endocrine system, many different types of cells can produce the same cytokine, and a single cytokine may act on a wide variety of target cells. Further, several cytokines may produce the same effect on a target, so the loss of one type of cytokine may have few if any consequences for the organism; this situation is called redundancy. Finally, the response of a target cell may be altered by the context in which it receives a cytokine signal. The context includes other cytokines in the milieu, and extracellular matrix. Thus has developed the concept of cytokines as alphabet letters that combine to spell words which make up a molecular language.
Types of cytokines
Cytokines may be divided into six groups: interleukins, colony-stimulating factors, interferons, tumor necrosis factor, growth factors, and chemokines.
Interleukins are proteins that are produced by one type of lymphocyte or macrophage and act on other leukocytes. At least 18 types of this important class, with varying origin and function, exist. Production of interleukins is now known not to be confined to lymphocytes or macrophages.
Colony-stimulating factors are produced by lymphoid and nonlymphoid cells. These factors provide a mechanism whereby cells that are distant from bone marrow can call for different types of hemopoietic progeny. There are also growth-promoting actions of locally produced colony-stimulating factors within the bone marrow to stimulate progenitors to differentiate into macrophages, granulocytes, or colonies containing both cell types.
Interferons classically interfere with the virus replication mechanisms in cells. Interferon-α (produced by leukocytes) and interferon-β (produced by fibroblasts) activate cytotoxicity in natural killer cells. Interferon-γ also activates natural killer cells, and is a potent activator of macrophages as well.
Tumor necrosis factor-α (TNF-α) is produced by a variety of cell types, but activated macrophages represent the dominant source. TNF-α activates natural killer cell cytotoxicity, enhances generation of cytotoxic T-lymphocytes, and activates natural killer cells to produce interferon-γ. TNF-α also acts on vascular endothelium to promote inflammation and thrombosis. TNF-α may also induce apoptosis in cells such as trophoblasts. TNF-β is a product of Th1 T-cells; in addition to providing help in proinflammatory cell-mediated immune responses, these cells produce delayed-type hypersensitivity reactions where macrophages are locally recruited and activated to kill intracellular pathogens, such as certain bacteria. TNF-β has interferon-type activity and a narrower spectrum of action than TNF-α.
Transforming growth factors (TGFs) have the ability to promote unrestrained proliferation of cells which otherwise has a benign behavior phenotype. These factors have therefore been implicated in development of cancer. There are two groups of transforming growth factors. TGF-α is a 5-kilodalton peptide produced by a variety of cells and collaborates with TGF-β, a 25-kD peptide, in promoting unrestrained tumorlike growth. TGF-β has potent pleiotropic effects on a wide variety of tissues and is a potent fibrogenic and immunosuppressive agent.
Chemokines are chemoattractant cytokines of small (7–14 kD) heparin-binding proteins that are subdivided into four families: CXC, CC, C, and CX3C. Chemokines are produced by macrophages stimulated by bacterial endotoxins, and control the nature and magnitude of cell infiltration in inflammation.
Wound healing is probably the most common phenomenon in which the importance of cytokines is seen. Cytokines ensure that the restorative sequences are carried out in the appropriate order by signaling blood cells and vascular endothelium to coagulate and fill in a wound opening, recruiting and signaling macrophages and neutrophils to engulf microbes, and guiding protective skin epidermal cells to grow over the wounded area. If the damage is more extensive, cytokines stimulate production of new skin cells, blood vessels (angiogenesis), connective tissue, and bone. See Cellular immunology