Newly Launched Recombinant Cytokines: IL-18, EGF, IL21, TNF-alpha, IL-1 beta

IL-18 is a pleiotropic pro-inflammatory cytokine. It belongs to the IL-1 superfamily and participates in both innate and acquired immunity. IL-18 mediates host immunity by regulating IFN-γ production in synergy with IL-12. IL18 also amplifies the innate immune response by other cytokines, such as GM-CSF, TNF-α, and IL-1β.

IL-18 activates downstream signal transduction in a similar fashion as IL-1β. IL18 binds with its receptor IL-18 receptor α. Following that, an accessory protein, IL-18Rβ, is recruited to the complex, and the downstream cellular signal is initiated. IL-18 signaling is negatively regulated by the secreted antagonist receptor IL-18BP.

Epidermal Growth Factor (EGF) is a protein responsible for stimulating cell growth, differentiation, and survival. By activating the EGF receptor signaling, it stimulates the growth of epidermal and epithelial tissues in vitro and in vivo. Many aggressive types of cancers have overactive EGF signaling. EGF is the founding member of the EGF family proteins that include HB-EGF, TGF-α, Betacellulin (BTC), Neuregulin-1 (NRG1), Neuregulin-2 (NRG2), Neuregulin-3 (NRG3), Neuregulin-4 (NRG4), and others. When EGF binds with its receptor, EGFR, EGFR dimerizes itself or with its homologs (Her2/ERBB2, HER3/ERBB3, or ErbB4). This activates the intracellular tyrosine kinase activity and stimulates the EGFR signaling cascade.

Interleukin 21 (IL-21) is an IL-2 family cytokine that strongly associated with inflammation and autoimmunity. It also exerts divergent effects on lymphoid cell leukemia and lymphomas. Clinical trials with IL-21 have yielded favorable results in cancer treatment, while the development of IL-21 inhibitors is in progress for treating autoimmune diseases. The biological functions of IL-21 are mediated via a heterodimeric receptor consisting of the IL-21R and the common γ-chain (γc/CD132) receptor. The latter is shared with other IL-2 family cytokines (IL‐4, IL‐7, IL‐9, IL‐15, and IL‐21).

Interleukin-1β (IL-1β), along with IL1-alpha and IL18, orchestrate the immune response through multiple downstream mechanisms. IL1-beta transduces its signal through binding with the receptor IL1RI, which is complexed with the accessory protein IL1RACP. IL1-beta signaling is negatively regulated by the decoy receptor IL1-RII, and the receptor antagonist IL1RA.

Tumour Necrosis Factor α (TNF-α) is an inflammatory cytokine responsible for necrosis or apoptosis, playing therapeutic roles in immunostimulation, infection resistance, embryonic development, and resistance to tumours. TNF-α exerts function by binding to TNFR-1 or TNFR-2 which belong to TNF receptor superfamily. FAS, CD40, CD27, and RANK are also members of TNF receptor superfamily