Interleukin-12 (IL-12) is a heterodimeric cytokine with a critical role in cell-mediated immunity. It stimulates the production of interferon-gamma (IFN-γ) from T cells and natural killer (NK) cells and promotes the differentiation of T helper 1 (Th1) cells.
IL-12 is a heterodimer of IL-12A and IL-12B linked through a disulfide-bond between cysteines in red in sequences below.
>IL-12 A
RNLPVATPDPGMFPCLHHSQNLLRAVSNMLQKARQTLEFYPCTSEEIDHEDITKDKTSTVEACLP
LELTKNESCLNSRETSFITNGSCLASRKTSFMMALCLSSIYEDLKMYQVEFKTMNAKLLMDPKRQ
IFLDQNMLAVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKLCILLHAFRIRAVTIDRVMSYLNAS.
>IL-12B
IWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITWTLDQSSEVLGSGKTLTIQVKEFGDAG
QYTCHKGGEVLSHSLLLLHKKEDGIWSTDILKDQKEPKNKTFLRCEAKNYSGRFTCWWLTTISTD
LTFSVKSSRGSSDPQGVTCGAATLSAERVRGDNKEYEYSVECQEDSACPAAEESLPIEVMVDAV
HKLKYENYTSSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDTWSTPHSYFSLTFCVQVQGK
SKREKKDRVFTDKTSATVICRKNASISVRAQDRYYSSSWSEWASVPCS.
Interleukin-12 (IL-12) is a heterodimeric cytokine composed of two subunits, p35 and p40, which are linked by disulfide bonds . This cytokine plays a crucial role in the regulation of immune responses, particularly in the differentiation of naive T cells into Th1 cells and the activation of natural killer (NK) cells .
IL-12 is a 70 kDa cytokine that is produced by various immune cells, including monocytes, macrophages, dendritic cells, neutrophils, and B cells . The recombinant form of human IL-12 (rHuIL-12) is typically produced in Chinese hamster ovary (CHO) cells that have been transfected with a fusion gene encoding the p35 and p40 subunits . This recombinant cytokine is biologically active and can be used in various research and therapeutic applications.
IL-12 is known for its pleiotropic effects on the immune system. It stimulates the production of interferon-gamma (IFN-γ) by NK and T cells, which in turn enhances the cytotoxic activity of these cells . IL-12 also promotes the proliferation of T cells and the differentiation of CD4+ T cells into Th1 cells, which are essential for cell-mediated immunity .
Recombinant human IL-12 has been investigated for its potential therapeutic applications in various diseases. It has shown promise as an adjuvant therapy in cancer treatment due to its ability to enhance the immune response against tumor cells . Additionally, rHuIL-12 is being developed as a medical countermeasure for the hematopoietic syndrome of acute radiation syndrome (HSARS), which occurs in individuals exposed to lethal radiation .
Clinical studies have demonstrated that low doses of rHuIL-12 can safely trigger hematopoietic and immune-mediated effects without causing significant toxicity . Common adverse events associated with rHuIL-12 administration include headache, dizziness, and chills . The cytokine’s elimination is biphasic, indicating significant distribution into extravascular spaces .