IL6 - Interleukin 6 | Elisa - Clia - Antibody - Protein

Background:

Interleukin-6 (IL-6) is a multifunctional cytokine belonging to the interleukin family.It plays a crucial role in regulating the immune response, inflammation, and hematopoiesis (formation of blood cells). IL-6 is produced by various cell types, including macrophages, T cells, B cells, fibroblasts, and endothelial cells, in response to infections, tissue injury, and other stimuli. IL-6 has diverse biological activities. It acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. Its functions include promoting the differentiation of B cells, stimulating the production of acute-phase proteins by the liver, regulating immune cell trafficking, and influencing the differentiation and proliferation of various cell types. IL-6 signals through a receptor complex consisting of the IL-6 receptor (IL-6R) and the glycoprotein 130 (gp130) subunit. The IL-6R can exist in both membrane-bound and soluble forms. The binding of IL-6 to the IL-6R activates downstream signaling pathways, such as the JAK-STAT pathway, which leads to the modulation of gene expression. Dysregulated IL-6 signaling is associated with various pathological conditions, including autoimmune diseases (such as rheumatoid arthritis and systemic lupus erythematosus), inflammatory diseases (such as inflammatory bowel disease), and certain cancers. Elevated levels of IL-6 have also been observed in conditions like cytokine release syndrome (CRS) and severe cases of COVID-19. Due to its involvement in inflammatory and autoimmune diseases, IL-6 has been targeted for therapeutic intervention. Drugs that inhibit IL-6 signaling, such as monoclonal antibodies targeting either IL-6 or the IL-6 receptor, are used to treat conditions like rheumatoid arthritis and cytokine release syndrome.

Protein Structure:

IL-6 is a glycoprotein with a molecular weight of approximately 26 kDa. It consists of 184 amino acids and has a four-helix bundle structure, which is typical of many cytokines. This structure allows it to bind specifically to its receptor and initiate signal transduction pathways.

Classification and Subtypes:

IL-6 belongs to the cytokine family, specifically the IL-6-type cytokine family, which includes IL-11, IL-27, leukemia inhibitory factor (LIF), oncostatin M (OSM), cardiotrophin-1 (CT-1), and ciliary neurotrophic factor (CNTF). These cytokines share a common receptor subunit, glycoprotein 130 (gp130), which is critical for signal transduction.

Function and Biological Significance:

IL-6 has pleiotropic effects, impacting various physiological and pathological processes:

• Immune Response: IL-6 stimulates the differentiation of B cells into antibody-producing plasma cells and promotes the growth of T cells. It also influences the production of acute-phase proteins by the liver, which are critical in the inflammatory response.
• Inflammation: IL-6 is a key mediator of the inflammatory response, contributing to the acute phase reaction. It induces the production of C-reactive protein (CRP) and fibrinogen while suppressing albumin synthesis.
• Hematopoiesis: IL-6 supports the growth and differentiation of hematopoietic stem cells and is involved in the regulation of megakaryocytes and platelet production.
• Metabolism: IL-6 plays a role in lipid metabolism, insulin resistance, and energy homeostasis.

Interactions:

• Receptors: IL-6 exerts its effects by binding to the IL-6 receptor (IL-6R), which exists in both membrane-bound (mIL-6R) and soluble (sIL-6R) forms. The IL-6/IL-6R complex then associates with gp130, initiating intracellular signaling cascades.
• Signaling Pathways: The binding of IL-6 to its receptor activates several signaling pathways, including the JAK/STAT pathway, MAPK pathway, and PI3K/Akt pathway. These pathways lead to the transcription of genes involved in inflammation, cell survival, proliferation, and differentiation.

Clinical Issues:

• Inflammatory Diseases: Elevated levels of IL-6 are associated with various inflammatory and autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease.
• Chronic Inflammation and Cancer: Chronic IL-6 signaling can contribute to cancer progression by promoting tumor cell survival, proliferation, angiogenesis, and metastasis. High IL-6 levels have been observed in multiple myeloma, prostate cancer, breast cancer, and colorectal cancer.
• Therapeutic Targets: IL-6 and its signaling pathways are therapeutic targets for several conditions. Tocilizumab, a monoclonal antibody against the IL-6R, is used to treat rheumatoid arthritis and other inflammatory diseases. Other IL-6 inhibitors are also being developed and tested for their efficacy in various diseases.

Summary:

Interleukin 6 (IL-6) is a pivotal cytokine with diverse roles in the immune response, inflammation, and hematopoiesis. It signals through a complex involving IL-6R and gp130, activating multiple intracellular pathways. IL-6 is implicated in various pathological conditions, including chronic inflammatory diseases and cancer, making it an important target for therapeutic intervention. Understanding IL-6's mechanisms and functions is essential for developing treatments for diseases characterized by dysregulated IL-6 activity