| Cytokines |
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Cytokines are a group of Protein s and Peptide s that are used in organisms as signaling compounds. These chemical signals are similar to Hormone s and Neurotransmitter s and are used to allow one Cell to communicate with another. The cytokine family consists mainly of smaller water-soluble Proteins and Glycoprotein s (proteins with an added sugar chain) with a mass of between 8 and 30 KDa . While hormones are released from specific organs into the blood and neurotransmitters are released by Nerve s, cytokines are released by many types of cells. They are particularly important in both innate and adaptive Immune Response s. Due to their central role in the immune system, cytokines are involved in a variety of immunological, inflammatory and infectious diseases. However, not all their functions are limited to the immune system, as they are also involved in several developmental processes during Embryogenesis . Cytokines are produced by a wide variety of cell types (both Haemopoietic and non-haemopoietic) and can have effects on both nearby cells or throughout the organism. Sometimes these effects are strongly dependent on the presence of other chemicals and cytokines. EFFECTS Each cytokine binds to a specific cell-surface receptor. Subsequent cascades of intracellular signalling then alter cell functions. This may include the upregulation and/or downregulation of several Genes and their Transcription Factors , in turn resulting in the production of other cytokines, an increase in the number of surface receptors for other molecules, or the suppression of their own effect by feedback inhibition. The effect of a particular cytokine on a given cell depends on the cytokine, its extracellular abundance, the presence/abundance of the complementary receptor on the cell surface, and downstream signals activated by receptor binding; these last two factors can vary by cell type. Interestingly, cytokines are characterized by considerable "redundancy", in that many cytokines appear to share similar functions. Generalization of functions is not possible with cytokines; nonetheless, their actions may be comfortably grouped as:
Cytokines binding to antibodies paradoxically have a stronger immune effect than the cytokine alone. This may lead to lower therapeutic doses and perhaps fewer side effects. Overstimulation of cytokines can trigger a dangerous syndrome known as a Cytokine Storm ; this may have been the cause of severe adverse events during a clinical trial of TGN1412 . NOMENCLATURE Cytokines have been variously named as Lymphokines , Interleukins and Chemokines , based on their presumed function, cell of secretion or target of action. Because cytokines are characterized by considerable redundancy and pleiotropism, such distinctions, allowing for exceptions, are obsolete.
Of note, IL-8 ( Interleukin-8 ) is the only chemokine originally named an interleukin. CLASSIFICATION Structural Structural homology has been able to partially distinguish between cytokines that do not demonstrate a considerable degree of redundancy so that they can be classified into four types:
Functional A more clinically and experimentally useful classification divides immunological cytokines into those that promote the proliferation and functioning of helper T-cells, type 1 ( IFN-γ etc.) and type 2 ( IL-4 , IL-10 , IL-13 , TGF-β etc.), respectively. A key focus of interestrole in the pathogenesis of autoimmune disorders. CYTOKINE RECEPTORS In recent years, the cytokine receptors have come to demand the attention of more investigators than cytokines themselves, partly because of their remarkable characteristics, and partly because a deficiency of cytokine receptors have now been directly linked to certain debilitating immunodeficiency states. In this regard, and also because the redundancy and pleiomorphism of cytokines are in fact a consequence of their homologous receptors, many authorities are now of the opinion that a classification of cytokine receptors would be more clinically and experimentally useful. A classification of cytokine receptors based on their three-dimensional structure has therefore been attempted. (It must be noted that such a classification, though seemingly cumbersome, provides with several unique perspectives for attractive pharmacotherapeutic targets.)
CYSTEINE-KNOT CYTOKINES Members of the Transforming Growth Factor Beta Superfamily belong to this group, including TGF-β1 , TGF-β2 and TGF-β3 . REFERENCES
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