Definition and properties of Interleukin-2

Interleukin-2 is a cytokine of the chemokine family.

It is derived from multicellular sources (mainly produced by activated T cells), and has multidirectional cytokines (mainly promotes lymphocyte growth, proliferation, and differentiation); it plays an important role in the body’s immune response and anti-viral infection. Can stimulate the proliferation of T cells that have been initiated by specific antigens or mitogenic factors; can activate T cells and promote cytokine production; stimulate NK cell proliferation, enhance NK killing activity and produce cytokines, and induce LAK cell production; Promote B cell proliferation and secrete antibodies; activate macrophages.

It can be used for clinical research and tumor treatment.

As of December 2013, at least 38 interleukins have been discovered, named IL-1 ~ IL-38 respectively. They are complex in function, form a network, and overlap in complexity.

General properties

1. IL-2 producing cells IL-2 is mainly synthesized by T cells (especially CD4 + T cells) stimulated by antigens or mitogens; B cells, NK cells and monocyte-macrophages can also produce IL-2.
2. IL-2 molecule IL-2 has a molecular weight of 15KD. It is a glycoprotein containing 113 amino acid residues and is encoded by a gene on chromosome 4 in humans. IL-2 has a certain species specificity. Human cells only respond to primate-derived IL-2, and almost all species of animal cells are sensitive to human IL-2.

3． IL-2 receptor (IL-2R) IL-2 target cells include T cells, NK cells, B cells, and monocyte-macrophages. IL-2R can be expressed on the surface of these cells. IL-2R contains three polypeptide chains: one is an α chain with a molecular weight of 55KD; one is a β chain with a molecular weight of 75KD; the other is a γ chain with a molecular weight of 64KD. The intracellular region of the α chain is shorter and cannot transmit signals to the cells, while the intracellular regions of the β chain and the γ chain are longer and have the ability to transmit signals. The three peptide chains alone have low binding affinity to IL-2, and only a simultaneous expression can produce a high affinity.

Biological activity

1. StimulateT cell growth T cells activated by various stimuli generally cannot survive long-term in vitro culture, and IL-2 can prolong their long-term continuous proliferation. Therefore, IL-2 was once named T cell growth factor (T cell growth factor, TCGF). The surface of resting T cells does not express IL-2R and has no response to IL-2; T cells can express IL-2R after being activated by mitogens or other stimuli and become IL-2 target cells; and IL-2 can be induced Target cells increase IL-2R expression. In vivo, the effect of IL-2 on CD4 + T cells is achieved through the autocrine pathway, because activated CD4 + T cells can produce large amounts of IL-2; while CD8 + T cells maintain cells through paracrine pathways Growth. The expression of IL-2R on T cells is transient, generally reaching a peak 2 to 3 days after activation and disappearing in about 6 to 10 days. With the disappearance of IL-2R, T cells lose their ability to respond to IL-2. Therefore, if you want to maintain normal T cells for long-term growth in vitro, you must constantly stimulate T cells with mitogens or other stimuli to maintain IL-2R expression.
2. Inducing cytotoxicity① CD8 + T cells that have received the pre-stimulation signal can be activated into CTL by the action of IL-2 and exert cytotoxic effects; under certain conditions, CD4 + T cells can also be induced by IL-2 Lethal effect. ②NK cells are the only lymphoid cells that normally express IL-2R, so they always remain reactive to IL-2. However, quiescent NK cells express only the β and γ chains of IL-2R, have low affinity for IL-2, and can only respond to high concentrations of IL-2. Once NK cells are activated, they express the α chain of IL-2R and become a high-affinity receptor; LAK activity induced by large doses of IL-2 is mainly NK cells. ③ Make T cells as NK cells to produce factors such as IFNγ, TNFβ and TGFβ to promote non-specific cytotoxins; also can induce the production of certain B cell growth factors and hematopoietic growth factors, etc., thereby exerting the corresponding biological effects.
3. Effect on B cellsIL-2 can promote the growth and differentiation of B cells. Activated or malignant B cells express high affinity IL-2R on the surface, but the density is lower; higher density IL-2 can induce B cell growth and reproduction, promote antibody secretion, and induce B cells to switch from secreted IGM to secreted IGG
4. Effects on macrophages The surface of human mononuclear-macrophages has a small amount of IL-2Rβ chain expression in normal fashion, but it can express high affinity IL-2R after being affected by IL-2, IFNγ or other activating factors. Mononuclear-macrophage cells are continuously enhanced by IL-2, their antigen presenting ability, bactericidal power, and cytotoxicity are significantly enhanced, and their ability to secrete certain cytokines is also enhanced.

Applied Research

Because IL-2 can induce and enhance cytotoxic activity, the application of IL-2 in the treatment of certain diseases, especially the treatment of tumors, has been extensively developed, using IL-2 alone or with LAK cells (see Chapter 4 for details) ) The combined use of tumor treatment has achieved a certain effect; it can also be used for the treatment of viral infections, immunodeficiency diseases and autoimmune diseases.

However, the side effects of IL-2 have also increasingly attracted people’s attention: IL-2 can cause general symptoms such as fever and vomiting, and can also cause disorders of water and salt metabolism and abnormal functions of the kidney, liver, heart, and lungs; the most common and serious It is the capillary leak syndrome that makes the patient have to stop treatment.

The side effects of IL-2 are often related to the dose of IL-2 and the time of medication. After stopping the medication, the symptoms are alleviated or disappeared quickly. The mechanism of side effects caused by IL-2 is multifaceted, but it is mainly indirect, that is, certain factors or killer cells induced by IL-2 play an important role; LAK cells are now known to dissolve intravascular tissues Causes multiple side effects. Give appropriate drugs (such as indomethacin, pethidine, acetaminophen, etc.), take combination medications, improve the mode of administration (such as a small amount of multiple short-term infusions) and the route of administration (such as changing systemic medication to Tumor local medication) etc. will effectively reduce adverse reactions.

ABOUT US

Profacgen is a state-of-the-art protein service provider located in Long Island, NY, USA. We provide custom protein services in the biological sciences, enabling access to the latest tools, techniques, and expertise with competitive pricing and rapid turnaround time. We serve a broad spectrum of industrial and academic clients with a commitment to delivering high-quality data and customer services. Here are some our products: maleimide peg amine, plasma protein fraction, pdgf bb molecular weight, activator protein, etc.