Interleukin-16 (IL-16)

IL-16, also known as interferon- γ Inducible factors are cytokines that play an important role in immune regulation.

Background information of IL-16

When IL-16 was first discovered, its inhibitory effect on LGL (large granular lymphocytes) was described through embedding method. This protein is synthesized by multiple cells, including activated lymphocytes, monocytes, and macrophages. The human IL-16 coding gene is located in the 9q21.3 region, and its atypical primer is in the exon of this gene, resulting in the synthesis of a primitive IL-16 protein with a molecular weight of 14 kda. The original IL-16 protein is an inactive precursor molecule that is activated through two enzymatic cleavage steps under stimuli such as innate immunity or bacterial or viral infections. The resulting IL-16 molecule is a single chain polypeptide with a molecular weight of 13000-14000 daq, composed of approximately 130 amino acid residues.

The Function of IL-16

IL-16 plays an important role in immune regulation. IL-16 can activate CD4+T cells and regulate the function of T cells in immune response. At the same time, IL-16 can also affect the proliferation and differentiation of white blood cells by inhibiting cell division and promoting the differentiation of megakaryocyte. Research has shown that IL-16 is involved in many immune and non-immune regulatory processes, including tumor immunotoxicity and inflammatory responses.

IL-16 related signaling pathway

IL-16 primarily exerts its biological function by binding to CD4 receptors. For example, the binding of IL-16 can alter the potential and permeability of cell membranes, thereby activating cells. Meanwhile, the binding of IL-16 and CD4 can also activate MAPK and PI3K signaling pathways.

IL-16 related diseases

IL-16 has been extensively studied in various diseases and their mechanisms, including autoimmune diseases, tumors, inflammation, and infections. Especially in the pathogenesis of autoimmune diseases, IL-16 plays an important role. IL-16 can promote the differentiation of CD4+T cells into relatively stable Th17 cells during the autoimmune process, which not only leads to autoimmune reactions but may also be related to the development and deterioration of autoimmune diseases.

In cancer, IL-16 has also been found to play an important role in the response to tumor microenvironment and immunotherapy. IL-16 can inhibit the proliferation and metastasis of tumor cells in the tumor microenvironment. In addition, IL-16 can also mediate the interaction between immune cytokines, further activating and regulating immune cell function, thereby enhancing immune response and accelerating tumor disappearance.

The potential application of IL-16 in medicine

Due to its important role in various immune, inflammatory, and tumor related processes, IL-16 has also received widespread attention in medicine. As one of the goals of therapeutic strategies, IL-16 can be achieved by interfering with its binding receptors or signaling pathways. At the same time, IL-16 can also be used as a biomarker for immune diagnosis, evaluating the disease status of patients by detecting its expression level, or as a targeted therapeutic drug for treating diseases.

List of investigational drugs related to IL-16

Niclosamide is a fish like antiparasitic drug that has recently been found to have therapeutic effects in CML by inhibiting IL-16 expression.

Maraviroc is an antagonist of CCR5 used in the treatment of HIV/AIDS. Research has shown that Maraviroc can also inhibit the release of IL-16, thereby protecting immune cells from the influence of inflammatory factors, and is expected to become a new drug for future immunotherapy.

INCB039110 is an oral small molecule targeted drug used for the treatment of multiple myeloma. INCB039110 has been proven to be a potent IL-16 and CD4 receptor antagonist.

AMG 592 is a small molecule drug for the treatment of osteoporosis fractures and a non-competitive IL-16 antagonist. It has been proven to inhibit the signaling pathway of IL-16 and prevent the activation of cytotoxic CD4+T cells.