Interleukin-18 (IL-18; also known as interferon-gamma inducing factor) is a proinflammatory cytokine that belongs to the IL-1 superfamily and is produced by macrophages and other cells. This cytokine can induce the IFN-gamma production of T cells. The combination of IL-18 and IL12 has been shown to inhibit IL4 dependent IgE and IgG1 production; and enhance IgG2a production of B cells. IL-18 binding protein (IL18BP) can specifically interact with this cytokine; and thus negatively regulate its biological activity. IL-18 is an IL-1−like cytokine that requires cleavage with caspase-1 to become active; was found to increase IgE production in a CD4+ T cells-; IL-4− and STAT6−dependent fashion. IL-18 and T cell receptor−mediated stimulation could induce naïve CD4+ T cells to develop into IL-4−producing cells in vitro. Thus; caspase-1 and IL-18 may be critical in regulation of IgE production in vivo; providing a potential therapeutic target for allergic disorders. IL-18 production in primary synovial cultures and purified synovial fibroblasts was; in turn; upregulated by TNF-α and IL-1β; suggesting that monokine expression can feed back to promote Th1 cell development in synovial membrane. Besides; synergistic combinations of IL-18; IL-12; and IL-15 may be of importance in sustaining both Th1 responses and monokine production in RA.
Interleukin-20 (IL-20) is a member of the IL-10 family of regulatory cytokines that includes IL-10, IL-19, IL-20, IL-22, IL-24 and IL-26. Members of this family share partial homology in their amino acid sequences but they are dissimilar in their biological functions. IL-20 exhibits approximately 28% amino acid identity with IL-10 and 76% amino acid identity with mouse IL-20. There are two heterodimeric receptor complexes for IL-20. The first is composed of IL-20 Rα and IL-20 Rβ. The second is composed of IL-22 R and IL-20 Rβ. Whereas the IL-22 R/IL-20 Rβ complex is shared with IL-24, the IL-20 Rα/IL-20 Rβ complex is shared with both IL-19 and IL-24. IL-20 has been shown to initiate transduction cascades involving STAT3 and stimulates the induction of pro-inflammatory genes including TNF-α and MCP-1. Initial functional studies using transgenic mice suggest that IL-20 has the ability to regulate skin development. The over-expression of both human and mouse forms of IL-20 results in keratinocyte hyper-proliferation, abnormal epidermal differentiation, and neonatal lethality. In humans, IL-20 and its receptors are up-regulated in psoriatic skin, and polymorphisms in the IL-20 gene have been associated with plaque-type psoriasis. IL-20 may also have a role in hematopoiesis. It enhances the proliferation of multi-potential progenitors in vitro and increases their numbers and cell cycling status in IL-20 transgenic mice. IL-20 is also shown to suppress COX-2 and PGE2 and acts as an inhibitor of angiogenesis in model systems.
IL-21 induces the production of IgG1 and IgG3 in B-cells. IL-21 may promote the transition between innate and adaptive immunity. IL-21 may have a role in proliferation and maturation of natural killer cells in synergy with IL15. IL-21 stimulates interferon gamma production in T-cells and natural killer cells by synergy with IL15 and IL18. Dysregulation of IL-21 has a role in multiple immune-mediated diseases including lupus, psoriasis and chronic inflammatory diseases.
IL21 belongs to the IL-15/IL-21 family. It is a cytokine with immunoregulatory activity. Cytokines are proteinaceous signaling compounds that are major mediators of the immune response. They control many different cellular functions including proliferation, differentiation and cell survival/apoptosis but are also involved in several pathophysiological processes including viral infections and autoimmune diseases. Cytokines are synthesized under various stimuli by a variety of cells of both the innate (monocytes, macrophages, dendritic cells) and adaptive (T- and B-cells) immune systems. IL21 is expressed in activated CD4-positive T-cells but not in CD8-positive T-cells, B-cells, or monocytes. It may promote the transition between innate and adaptive immunity. IL-21 has been tried as therapy for alleviating allergic responses. It can significantly decrease pro-inflammatory cytokines produced by T cells in addition to decreasing IgE levels in a mouse model for rhinitis (nasal passage inflammation)
Interleukin-22(IL-22) is a member of a group of the IL-10 family; a class of potent mediators of cellular inflammatory responses. IL-22 is produced by activated DC and T cells. IL-22 and IL-10 receptor chains play a role in cellular targeting and signal transduction. It can initiate and regulate innate immune responses against bacterial pathogens especially in epithelial cells such as respiratory and gut epithelial cells. IL-22 along with IL-17 likely plays a role in the coordinated response of both adaptive and innate immune systems. IL-22 also promotes hepatocyte survival in the liver and epithelial cells in the lung and gut similar to IL-10. Biological activity of IL-22 is initiated by binding to a cell-surface complex consisting of IL-22R1 and IL-10R2 receptor chains. IL-22 biological activity is further regulated by interactions with a soluble binding protein; IL-22BP. IL-22BP and an extracellular region of IL-22R1 share sequence similarity. In some cases; the pro-inflammatory versus tissue-protective functions of IL-22 are regulated by cytokine IL-17A.
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