Cytokines & Chemokines

Interleukin-4 (IL-4) is a pleiotropic cytokine that regulates diverse T and B cell responses including cell proliferation; survival and gene expression. IL-4 is produced by mast cells; T cells; and bone marrow stromal cells. IL-4 regulates the differentiation of naive CD4+ T cells into helper Th2 cells; characterized by their cytokine-secretion profile that includes secretion of IL-4; IL-5; IL-6; IL-10; and IL-13; which favor a humoral immune response. Another dominant function of IL-4 is the regulation of immunoglobulin class switching to the IgG1 and IgE isotypes. Excessive IL-4 production by Th2 cells has been associated with elevated IgE production and allergic response.

Interleukin-3 (IL-3) is a potent growth promoting cytokine. IL-3 can stimulate the proliferation and differentiation of pluripotent hematopoietic stem cells as well as various lineage committed progenitors. IL-3 exerts its biological function through binding to specific cell surface receptors. The amino acid sequences of this protein among different species share relatively low identity and its activity is highly species-specific. IL-3 has also been shown to possess neurotrophic activity; and is thought to be associated with neurologic disorders.

Interleukin 12 (IL-12) is the founding member of the IL-12 family of heterodimeric cytokines, which have important immunological functions. IL-12 is composed of two disulfide-linkedsubunits of 35 kDa and 40 kDa, respectively. The 35 kDa subunit (p35) is an α-helical protein homologous to IL-6 and GCSF.The 40 kDa subunit(p40) contains one fibronectin type III and one Ig C2-like domain, and has a high degree of structural homology to type I cytokine receptors. Whereas p35 subunit is unique to IL-12,the p40 subunit is also utilized in IL-23.Mature rat p35 is a 194 amino acids (aa) protein that is secreted as a heterodimer linked to p40. It contains three potential N-linked glycosylation sites and shares 86%, and 58% aa sequence identity with mouse and human p35, respectively. Mature rat p40 contains 313 aa and can exist in multiple forms, including monomer, homodimer, heterodimer linked to p19 (forming IL23), and heterodimer linked to p35 (forming IL-12). IL12 facilitates hematopoietic st

Associates with IL23A to form the IL-23 interleukin, a heterodimeric cytokine which functions in innate and adaptive immunity. IL-23 may constitute with IL-17 an acute response to infection in peripheral tissues. IL-23 binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R, activates the Jak-Stat signaling cascade, stimulates memory rather than naive T-cells and promotes production of pro-inflammatory cytokines. IL-23 induces autoimmune inflammation and thus may be responsible for autoimmune inflammatory diseases and may be important for tumorigenesis. Cytokine that can act as a growth factor for activated T and NK cells, enhance the lytic activity of NK/lymphokine-activated killer cells, and stimulate the production of IFN-gamma by resting PBMC.