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Interleukins

Interleukins are a diverse family of secreted proteins and signal molecules which are vital mediators of physiological responses to many infections, they have also been found to contribute significantly to the pathophysiology of a large number of disorders.

Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) which are vital in performing many complex immunomodulatory functions such as cell proliferation, differentiation, activation, migration and maturation. They were originally identified to be expressed by white blood cells (leukocytes), a large number of interleukins are now synthesised by helper CD4 T lymphocytes, endothelial cells, monocytes and macrophages. Interleukins can initiate a response through the interaction/binding to high-affinity receptors that are located on the cell surface, they have the ability to function either as an autocrine or paracrine fashion. The response generated by a particular cell to these cytokines is largely dependent on the ligands that are involved, the specific receptors that are expressed on the cell surface and which signalling cascades have been activated.

Interleukins can exert both inflammatory and anti-inflammatory actions/responses. There are also some family members that can function as chemo-attractants for helper T cells and parallel the actions of certain chemokines. ILs are essential mediators of a physiological response to specific infections and can significantly contribute to the pathophysiology for a diverse range of disorders. This allows interleukins to be used as potential therapeutic targets.

The key features of interleukins include

  1. Interleukins represent a broad family of biologically active proteins that possess a hormone‐like actions in order to regulate the functions, development, differentiation and proliferation of cells of the haematopoietic and immune systems.
  2. Cell surface receptors are responsible for mediating the activities of interleukins and binding to these receptors triggers gene induction through the activation of various intracellular signalling pathways.
  3. Interleukins have the ability to display complex in vivo biological interactions among themselves or with other molecular mediators.
  4. The immune‐stimulatory and pro-inflammatory activities which are exhibited by interleukins can be vital for host cell defence against foreign pathogens.
  5. Biological properties of interleukins indicates their potential for developing as biopharmaceuticals (therapeutic drugs) which can be used against chronic diseases and infections. However, at present only a handful have been proven clinically useful.

COMMON TYPES OF INTERLEUKINS

  • Interleukin-1: There are two types of IL-1 (IL-1 alpha and IL-1 beta) that are involved in the regulation of inflammatory reactions, hematopoiesis and immune responses.
  • Interleukin-2: IL-2 are known to be secreted by lectin- or antigen-stimulated T cells and these are responsible for regulating the growth and differentiation T cells and certain B cells. It is also a lymphokine which can induce the proliferation of responsive T cells.
  • Interleukin-3: IL-3 is produced by T lymphocytes and T-cell lymphomas following the stimulation with mitogens, antigens or chemical activators. One of its main function is to regulate hematopoiesis through controlling the function, production and differentiation of macrophages and granulocytes.
  • Interleukin-4: IL-4 can be produced from CD4+T cells specialized through helping B cells in order to proliferate and to then undergo a class switch recombination and somatic hyper mutation. Th2 cells are able to use IL-4 to carry out an important function during B-cell responses which can involve class switch recombination to the IgG1 and IgE isotypes.
  • Interleukin-5: IL-5 which can also be called eosinophil differentiation factor (EDF) is a specific cytokine for eosinophilpoiesis, it is vital in regulating activation and growth of eosinophil and therefore play a crucial role in diseases which are linked with an increased levels of eosinophils (for example asthma).
  • Interleukin-6: IL-6 that is also commonly known as interferon beta-2 and B-cell stimulatory factor-2 (BSF-2) has an main function in the final differentiation of B cells into immunoglobulin-secreting cells, it is also vital in inducing plasmacytoma/ myeloma growth, acute-phase reactants and nerve cell differentiation. It is involve in many different biological functions.
  • Interleukin-7: IL-7 serves as a growth factor for early lymphoid cells of both B- and T-cell lineages. It also seems to be evolutionary related to IL-9.
  • Interleukin-8: IL-8 can also be called CXCL8 and can be produced by mainly macrophages and many other cell types for example endothelial, epithelial and airway smooth muscle cells. It can function to induce chemotaxis in target cells and then also induce phagocytosis.
  • Interleukin-9: IL-9 is a cytokine which is importing in supporting IL-2 and IL-4 independent growth of helper T cells. It is also evolutionary related to IL-7.
  • Interleukin-10: IL-10 is a protein that can inhibit the synthesis of many cytokines for example IL-2, IL-3, GM-CSF, IFN-gamma and TNF.
  • Interleukin-11: IL-11 is essentially a secreted protein which is able to stimulate mega karyocytopoiesis and this can result in elevating the production of platelets or activating osteoclasts and inhibiting the epithelial cell proliferation, apoptosis and macrophage mediator production. These functions are all vital in mediating mucosal protective effects, hematopoietic and osseous.
  • Interleukin-12: IL-12 (IL-12 P40 and IL-12 P70) is involved in the maintenance and stimulation of Th1 cellular immune responses, also has important roles in pathological Th1 responses (e.g. bowel disease or multiple sclerosis) and in enhancing the cytotoxic function of NK cells.
  • Interleukin-13: IL-13 is a critical pleiotropic cytokine which is vital in the regulating many inflammatory and immune responses. It also has the ability in inhibiting inflammatory cytokine production and synergises with IL-2 in order to regulate interferon-gamma synthesis.
  • Interleukin-15: IL-15 possesses a number of different biological functions such as maintaining and stimulating cellular immune responses, it stimulates the synthesis of T lymphocytes via the interaction of IL-15 with components of IL-2R.
  • Interleukin-16: IL-16 is predominately by mononuclear phagocytes (in particular macrophages that have been infected by viruses). It can target T cells and activated B cells and one of its main function is to induce the production of natural killer cells.
  • Interleukin-17: IL-17 is a potent pro-inflammatory cytokine that can be produced by activated memory T cells. It also represent a unique signalling pathway that in highly conserved among vertebrates.
  • Interleukin-18: IL-18 are cytokines that are produced by macrophages and are vital in targeting NK cells and Th1 cells. It has an important function in inducing the production of IFN-gamma and also to increase the activity of NK cells.
  • Interleukin-22: IL-22 is produced from T helper 17 cells (Th17). It has many roles which include activating STAT1 and STAT3, stimulating the production of defensins from epithelial cells and increasing the production of acute phase proteins (SAA, heptaglobin and alpha 1-antichymotrypsin).

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