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Interleukin (IL) is a lymphokine that interacts between leukocytes or immune cells, and it belongs to the same group of cytokines as the hematopoietic growth factor. They coordinate and interact with each other to perform hematopoietic and immunoregulatory functions. IL plays an important role in transmitting information, activating and regulating immune cells, mediating T and B cell activation, proliferation and differentiation, and inflammatory responses. Thirty-eight ILs have been identified, named IL-1 to IL-38. Because of their significant anti-tumor cell effects, IL2 and IL11 are commonly used clinically to target tumor patients for immunotherapy.
Figure 1. Interleukin‑1 family members, processing, receptors and regulation. (Sims J E, et al., 2020)
IL-1 is mainly produced by activated monocyte macrophages and belongs to the IL-1 family, which includes 11 ILs. IL-1 is one of the important inflammatory mediators and a pyrogenic component with thermogenic and inflammation-mediating effects. It plays a regulatory role mainly in cellular immune activation. In rheumatoid arthritis, IL-1 is involved in the process of pathological damage to synovium and cartilage, and high levels of IL-1 can be measured in the joint fluids of a variety of arthritis. In addition, studies have shown that IL-1 plays a regulatory role in post-injury repair of the nervous system and that the level of concentration of IL-1 at the site of injury directly affects the repair of damaged neuronal cells or induces apoptosis.
IL-2 is mainly produced by T cells and its main biological function is to stimulate T cell growth. Because IL-2 can induce and enhance cytotoxic activity, research on the application of IL-2 for the treatment of certain diseases, especially for the treatment of tumors, is now widely carried out. The use of IL-2 alone in the treatment of tumors has achieved certain efficacy and is also expected to be used in the treatment of viral infections, immunodeficiency diseases, and autoimmune diseases.
IL-3 is a major early hematopoietic growth factor and plays an extremely important role in hematopoietic regulation. Because of its stimulatory effect on the growth of bone marrow stromal cells, IL-3 is essential for the reconstruction of the hematopoietic microenvironment after allogeneic bone marrow transplantation. IL-3 in combination with GM-CSF optimally stimulates the production of hematopoietic cells and platelets and can rebuild the function of the bone marrow in the case of myelosuppression induced by chemotherapy and radiotherapy, as well as improve the state of aplastic anemia.
IL-4 is a growth factor secreted by T-cells themselves and is important for the development of T and B lymphocytes as well as driving humoral immune responses and antibody production. Studies have demonstrated that IL-4 can inhibit IL-1, IL-6, and TNF secretion and maybe a new target for the treatment of septic shock. Clinically, IL-4 has shown significant efficacy in the treatment of both Hodgkin's disease and chronic lymphocytic leukemia.
IL-6 is mainly produced by monocyte macrophages, Th2 cells, vascular endothelial cells, and fibroblasts. IL-6 can regulate the growth and differentiation of a variety of cells, and can regulate the immune response, the acute phase response, and hematopoietic function, as well as playing an important role in the body's anti-infection immune response. Studies have found that dysregulation of IL-6 expression can cause autoimmune diseases, tumors, neurological disorders, etc., and its clinical manifestations mainly include increased IL-6 levels at the onset of the disease.
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