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Introduction to Some IL Antibodies

Published on 3/13/2019
For additional information  Click Here

What is IL?

 

Interleukin (IL) is a kind of cytokine produced by many kinds of cells and used in many kinds of cells. It was originally discovered that leucocytes were produced and regulated from one cell to another, hence its name. IL now refers to a group of cytokines whose molecular structure and biological functions have been basically clear and have important regulatory roles. IL plays an important role in transmitting information, activating and regulating immune cells, mediating activation, proliferation and differentiation of T and B cells, and in inflammatory reaction. It is a member of the lymphokine family and is produced by lymphocytes and macrophages.

In the course of the research on immune response, researchers found that there were many bioactive molecules in cell culture supernatants treated with various stimulants, named after the measured activity. Over the past decade, nearly a hundred factors have been reported. Later, comparative studies using molecular biology techniques found that many factors named after biological activities in the past can actually play a variety of biological effects of the same-substance.

Today let us learn some antibodies about IL.

  1. 1.Canakinumab

Recombinant monoclonal antibody to Human IL1 beta. Canakinumab (INN, trade name Ilaris, previously ACZ885) is a human monoclonal antibody targeted at interleukin-1 beta. It has no cross-reactivity with other members of the interleukin-1 family, including interleukin-1 alpha. Canakinumab was for the treatment of rheumatoid arthritis. Canakinumab is as a possible treatment for chronic obstructive pulmonary disease, gout and coronary artery disease.

IL-1

 

Interleukin-1 (IL-1) is also known as lymphocyte stimulating factor. It is mainly produced by activated mononuclear-macrophages.

Structure: There are two different molecular forms of IL-1 molecule. One is called IL-1alpha, which is composed of 159 amino acids, the other is called IL-1beta, which contains 153 amino acids. They are encoded by different genes. Although the amino acid sequence is only 26% homologous, IL-1alpha and IL-1beta bind to the same cell surface receptor with the same affinity and play the same biological role.

Function: Local low concentration can stimulate the activation of APC and T cells, promote the proliferation of B cells and secrete antibodies, and regulate immunity. When produced in large quantities, it has endocrine effects: inducing protein synthesis in the acute phase of the liver, causing fever and cachexia.

Biological activity: 1. Local low concentration of IL-1 mainly plays an immunoregulatory role. 2. Animal experiments of systemic effects have proved that the secretion or injection of IL-1 can induce systemic reactions through blood circulation.

  1. Mepolizumab

Recombinant monoclonal antibody to Human IL5. Mepolizumab (proposed trade name Bosatria) is a humanized monoclonal antibody that recognizes interleukin-5 (IL-5), and is used to treat certain kinds of asthma and white blood cell diseases. Recent studies have concluded that mepolizumab may improve exacerbations in patients with severe eosinophilic asthma, an adult-onset asthma which represents less than 5% of all asthma. IL-5 is a chemical messenger in the immune system that stimulates the growth of eosinophils. In eosinophilic asthma, eosinophils are present in the lungs. When mepolizumab was given to people with eosinophilic asthma, it eliminated eosinophils from the bloodstream, and reduced eosinophils in the lungs and bone marrow. Mepolizumab also reduced the number of asthma exacerbations, and reduced the need for corticosteroids.

IL-5

Structure: IL-5 is produced by CD4 + T cells activated by antigen, and mast cells can also produce IL-5. The molecular weight of natural IL-5 is 40-50KD, which is a dimer glycoprotein linked by disulfide bond, but the monomer IL-5 also has IL-5 activity.

Function: IL-5 was once called T cell replacement factor (TRF), but it was found that human IL-5 had no obvious stimulating effect on B cells. Its main function was to stimulate the proliferation, differentiation and activation of eosinophils. IL-5 not only increases the number of eosinophils, but also enhances their functions. The increase of eosinophils in worm infections and allergic diseases is mainly caused by IL-5. Human IL-5 also promotes basophils to release inflammatory mediators such as histamine and leukotrienes, thereby enhancing basophil activity.

  1. Sarilumab

Sarilumab is a recombinant human monoclonal antibody expressed in CHO binding to human IL6. Anti-Human IL6 Therapeutic Antibody is a human monoclonal antibody against the interleukin-6 receptor for the treatment of rheumatoid arthritis.

IL-6

Structure: Human IL-6 gene is located on chromosome 7, and the molecular weight of IL-6 is between 21 and 30 KD.

Function: Monocyte macrophages, Th2 cells, vascular endothelial cells and fibroblasts are the main products. It can stimulate the proliferation of activated B cells, secrete antibodies, stimulate T cell proliferation and CTL activation, stimulate hepatocytes to synthesize acute phase proteins, participate in inflammatory response, and promote the development of blood cells.

IL-6 can be synthesized by a variety of cells, including activated T and B cells, monocytes-macrophages, endothelial cells, epithelial cells and fibroblasts.

  1. Ustekinumab

Recombinant monoclonal antibody to IL12+IL23. Ustekinumab (INN, experimental name CNTO 1275, proprietary commercial name Stelara, Centocor) is a human monoclonal antibody. It is directed against interleukin 12 and interleukin 23, naturally occurring proteins that regulate the immune system and immune-mediated inflammatory disorders.

IL-12

Structure: IL-12 is mainly produced by B cells and macrophages. Its molecule is a heterodimer. Two subunits of 40 KD (p40) and 35 KD (p35) are linked by disulfide bonds.

Function: IL-12 mainly acts on T cells and NK cells. It has been named cytotoxic lymphocyte maturation factor (CLMF) and NK cell stimulating factor (NKsf). IL-12 can stimulate the proliferation of activated T cells and promote the differentiation of TH0 cells into TH1 cells; induce the cytotoxic activity of CTL and NK cells and promote their secretion of IFN-gamma, TNF-alpha, GM-CSF and other cytokines; promote the expression of NK cells and IL-2ralpha, TNF receptors and CD56 molecules, and enhance the ADCC effect on tumor cells.

IL-13

Structure: IL-13 is produced by TH2 cells and its molecular weight is about 10 KD.

Functions: IL-13 can induce the differentiation of monocytes and enhance the expression of MHC class II molecules; inhibit the secretion of monocyte factors induced by LPS and control inflammation; induce the proliferation of B cells and synthesis of IgE antibodies, enhance the expression of MHC class II molecules, CD23 and CD72 on the surface of B cells; cooperate with IL-2 to stimulate the production of IFN by NK cells, thereby promoting the activation of monocyte-macrophage and the immune response of TH1 cells. Recently, it has been found that IL-13 also has many functions, such as inhibiting HIV-1 replication in macrophages, inducing IL-1RA gene expression and protein synthesis in neutrophils.

  1. Perakizumab

Recombinant Humanized (from mouse) antibody to Human IL17A. Perakizumab (INN) is a humanized monoclonal antibody designed for the treatment of arthritis. It binds to IL17A and acts as an immunomodulator.

IL-17

Function: IL-17 is the main effector of Th17 cells. It is secreted by CD4 + T cells. It can induce the synthesis and secretion of IL-6, IL-8, G-CSF and PGE2 by epithelial cells, endothelial cells and fibroblasts, and promote the expression of ICAM-1.

It has been found that IL-17 is a T cell-derived cytokine. The family consists of six ligands (IL-17A~IL-17F) and five receptors (IL-17RA~IL-17RD and SEF). IL-17 is an inflammatory cytokine produced mainly by activated T cells.

IL-17 is an early initiator of T cell-induced inflammatory response, which can be amplified by promoting the release of pro-inflammatory cytokines. When IL-17 binds to receptors, it can play its biological role through the pathway of MAP kinase and nuclear factor kB (NF-kB). Th17 cells can secrete and produce IL-17A, IL-17F, IL-6 and a tumor necrosis factor (TNF-a), which can mobilize, recruit and activate neutrophils collectively. IL-17 produced by Th17 cells can effectively mediate the excitation process of neutrophil mobilization, thereby effectively mediating the inflammatory response of tissues.

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