Interferon-γ is a potent multifunctional cytokine which is secreted primarily by activated NK cells and T cells. Originally characterized based on anti-viral activities, IFN-γ also exerts anti-proliferative, immunoregulatory, and proinflammatory activities. IFN-γ can upregulate MHC class I and II antigen expression by antigen-presenting cells.

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IL-2 was discovered through its function as a T cell growth factor (TCGF), and plays a pivotal role in immune responses against pathogenic infection. Recognition and binding of the foreign Ags by the TCRs stimulate both the secretion of IL-2 and the expression of IL-2Rs on the T cell surface. Subsequently, the IL-2/IL-2R interaction activates the intracellular Ras/Raf/MAPK, JAK/STAT, and PI3K/AKT signal pathways, and ultimately stimulates the growth, differentiation, and survival of the Ag-selected cytotoxic T cells. Human IL-2 acts on murine and human T cells, and its receptors are shared by others cytokines. IL-2Ra is an IL-2–specific receptor, IL-2Rb is shared with IL-15 and the gc is a common receptor shared by many cytokines including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21.

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IL-4 is the primary cytokine implicated in the development of Th2-mediated responses, which is associated with allergy and asthma. The Type I receptor comprises IL-4Rα and the common gamma-chain (γc), which is also shared by the cytokines IL-2, -7, -9, -15 and -21 and is present in hematopoietic cells. IL-4 can use the type II complex, comprising IL-4Rα and IL-13Rα1, which is present in non-hematopoietic cells. This second receptor complex is a functional receptor for IL-13, which shares approximately 25% homology with IL-4. The type I receptor complex can be formed only by IL-4 and is active in Th2 development. In contrast, the type II receptor complex formed by either IL-4 or IL-13 is most active during airway hypersensitivity and mucus secretion and is not found in T cells.

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Human SDF-1 belongs to the CXCL chemokine family. SDF is expressed by many organs, most abundantly in pancreas, spleen, ovary and small intestine. SDF-1 (CXCL12) and its receptor CXCR4 are involved in regulation of migration, survival, and development of multiple cell types, including human hematopoietic CD34+/CD38-/low and stromal STRO-1+ stem cells. Stress-induced modulations in SDF-1 and CXCR4 levels participate in recruitment of immature and maturing leukocytes from the BM reservoir to damaged organs as part of host defense and repair mechanism. The SDF-1/CXCR4 system is involved in the establishment of organ metastasis in different cancers. Recently, several studies have demonstrated the existence of a small subset of cancer cells which share many characteristics with stem cells and named cancer stem cells (CSC). They constitute a reservoir of self-sustaining cells with the ability to maintain the tumor growth. Most of them express CXCR4 receptor and respond to a chemotactic gradient of SDF-1, suggesting that CSC probably represent a subpopulation capable of initiating metastasis.

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SCF (KITL) is a hematopoietic growth factor, and it can synergize with a number of other cytokines to stimulate growth of hemopoietic progenitors in vitro and stimulates blood cell production in vivo. SCF is encoded by Sl ('steel'), a gene critical to the development of several distinct cell lineages during embryonic life. KITL was identified as a soluble protein; nevertheless, the predicted amino acid sequence indicates that it is an integral transmembrane protein. KITL is generated by proteolytic cleavage from a transmembrane precursor. Dysregulation of SCF–KI signaling and gain-of-function KIT mutations contribute to the genesis of many cancers, with acute myeloid leukemia, gastrointestinal stromal tumors and mastocytosis being the most prevalent types.

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IL-6 is a multifunctional cytokine that can regulate various immune and inflammatory responses. Several studies have suggested a crucial role for IL-6 in angiogenesis. IL-6 has been shown to cause proliferation and migration of systemic endothelial cells in culture. The classical responsiveness to IL-6 is governed by a receptor complex consisting of two membrane-bound subunits, an 80-kD cognate chain (IL-6R), and a ubiquitously expressed 130-kD β-chain receptor (gp130) which acts as the universal signal-transducing element for all IL-6 family cytokines. Alternatively, IL-6 regulation of leukocyte trafficking relies upon signaling via its soluble IL-6R (termed IL-6 trans-signaling). IL-6 plays a major role in regulating neutrophil clearance during acute peritoneal inflammation; as a result of specific down-regulation of neutrophil-attracting chemokine (CXCL1/KC) production. IL-6 is a key factor that reciprocally regulates Th17 and Foxp3(+) Treg differentiation by inhibition of TGF-beta induced Foxp3 and induction of RORγt, a Th17 lineage-specific transcription factor.

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TNF-α is secreted by macrophages, monocytes, neutrophils, T-cells (principally CD4+), and NK-cells. Many transformed cell lines also secrete TNF-α. TNF-α forms multimeric complexes; stable trimers are most common in solution. A 26 kD membrane form of TNF-α has also been described. TNF-α binding to surface receptors elicits a wide array of biologic activities including: cytolysis and cytostasis of many tumor cell lines in vitro, hemorraghic necrosis of tumors in vivo, increased fibroblast proliferation, and enhanced chemotaxis and phagocytosis in neutrophils.

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