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TH2 and Anti-Inflammatory Cytokines See also signal transduction See also factors affecting Th1/Th2 development See also cytokines secreted during Th development Th2 cells secret IL-4, IL-10 and IL13, which promote humoral immunity. IL-4 and IL-10 are considered the major anti-inflammatory cytokines. They promote humoral immunity by stimulating the growth and activation of mast cells and eosinophils, the differentation of B cells into antibody-secreted B cells, and B cell immunoglobulin switching to IgE. Importantly, these cytokines inhibit macrophage activation, T-cell proliferation and the production of pro-inflammatory cytokines. IL-1α IL-1β IL5 IL-5 is a Th2 cytokines essential for the growth and differentiation of eosinophils. It is also a B-cell growth factor in mice (but not in humans). IL-5 is a well known cytokine generally detected in allergic diseases and produced by Th2, mast cells and eosinophils. IL-5 is also an enhancing factor for MDC production by APCs. IL9 IL-9 is a T cell and mast cell growth factor that can also potentiate IL-4-induced IgG4 and IgE production. IL13 IL-13 is produced by mononuclear phagocytes and shares several features with IL-4. Decreased plasma levels of IL-13 has been associated in progressive HIV-1 infection, whereas HAART + IL-2 therapy increased IL-13 plasma levels. Both IL-13 (as well as IL-4) regulate the humoral immune response by stimulating the proliferation and survival of B cells and triggering Ig class switching. IL15 IL-15 is a T cell growth factor whose effects include T cell proliferation, enhanced cytotoxicity of T cell and natural killer cells, B cell proliferation, and immunoglobulin secretion. IL-15 shares with IL-2 the By chains of the receptor complex, although is mostly secreted by macrophages and NK cells and not by activated T cells as with IL-2. IL16 IL-16, formerely known as lymphocyte chemoattractant factor, is a multifunctional cytokine. It is a chemoatractant that inhibits lymphocyte activation and may also inhibit HIV replication. TGF-B: (transforming growth factor-B) induces growth arrest. This important mediator is strongly induced when most cell types encounter apoptotic cells. It is synthesized, released and activated in response to the apoptotic cell and is a chief participatnt in the normal dampening of inflammation. It suppresses the production of a wide array of inflammatory cytokines and chemokines such as MCP-1 that are invovled in attracting mononuclear phagocytes. T cells are influenced by TGFB at all stages of their development. It inhibts T cell proliferation, cytokine production and cytotoxicity. However, similar to IL-10, a it also has some positive effects on T cell function via inhibition of T cell apoptosis, enhancement of native T cell proliferation and induction of cytokines. IL21 IL-21 is a cytokine produced by activated T cells, and its receptor (IL-21R) is expressed in lymphoid tissues, in particular on NK, B, T and DCs, as well as macrophages. IL-21 is structurally related to the cytokines IL-2 and IL-15 and signals through a receptor complex requring the common y-chain similar to the IL-2R and IL-15R. IL21 has been reported to promote the maturation of NK cell progenitors from bone marrow; however, in contrast to IL-2 and IL-15, treatmetn wil IL-21 limits mature NK cell prolfieration. Although IL-21 does not increase the overall NK cell population, it has been shown to augment the functional maturation of NK effector functions, such as cytokine production and cytotoxicity. Il-21 also activates CD8+ T cells and promotes tumor Ag-specific activaiton and clonal expanion of specific CD8+ T cells. IL21 stimulated CD8+ T cells have nhanced survival and cytotoxic respondes compared with CD8+ T cells stimulated with IL-2. By potentiiating the effector function sof NK and cD8+ T cells, IL-21 enhances both the innate and adaptive componetns of tumor immunity and promotes the tumor-free survival of treated mice. IL-21 is a cytokine that regulates the activation of T and NK cells and promotes the proliferation of B cells activated via CD40. TGF-β Although not specifically classified as a Th2 cytokine, TGF-beta is a potent anti-inflammatory cytokines influencing cell cycle, differentiation, wound healing, angiogenesis and apoptosis. It is secreted by several cell types, including hemopoietic, endothelial, and connective tissue cells and it is stored by the extracellular matrix. It suppresses B and T cell proliferation and the cytolytic activity of NK cells, and stimulates fibroblast proliferation and collagen synthesis. Transforming growth factor-β can activate NF-kB. |
