Structure
This gene encodes a cytokine that functions in inflammation and the maturation of B cells. In addition, the encoded protein has been shown to be an endogenous pyrogen capable of inducing fever in people with autoimmune diseases or infections. The protein is primarily produced at sites of acute and chronic inflammation, where it is secreted into the serum and induces a transcriptional inflammatory response through interleukin 6 receptor, alpha. Elevated levels of the encoded protein have been found in virus infections, including COVID-19 (disease caused by SARS-CoV-2).
Gene Ontology (GO) annotations related to this gene include signaling receptor binding and growth factor activity.
Three dimensional structures for IL6 Gene
Function
Diseases associated with IL6 include Kaposi Sarcoma and Rheumatoid Arthritis, Systemic Juvenile. Among its related pathways are Apoptotic Pathways in Synovial Fibroblasts and MIF Mediated Glucocorticoid Regulation.
IL6 is a cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. It binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the intracellular IL6-signaling pathway (Probable).
The interaction with the membrane-bound IL6R and IL6ST stimulates 'classic signaling', whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'.Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells (Probable).
IL6 is a potent inducer of the acute phase response.
Rapid production of IL6 contributes to host defense during infection and tissue injury, but excessive IL6 synthesis is involved in disease pathology.
In the innate immune response, IL6 is synthesized by myeloid cells, such as macrophages and dendritic cells, upon recognition of pathogens through toll-like receptors (TLRs) at the site of infection or tissue injury (Probable).
In the adaptive immune response, IL6 is required for the differentiation of B cells into immunoglobulin-secreting cells.
IL6 plays a major role in the differentiation of CD4(+) T cell subsets. It is essential factor for the development of T follicular helper (Tfh) cells that are required for the induction of germinal-center formation. It required to drive naive CD4(+) T cells to the Th17 lineage. Also required for proliferation of myeloma cells and the survival of plasmablast cells (By similarity).
IL6 acts as an essential factor in bone homeostasis and on vessels directly or indirectly by induction of VEGF, resulting in increased angiogenesis activity and vascular permeability.IL6 induces, through 'trans-signaling' and synergistically with IL1B and TNF, the production of VEGF.
Involved in metabolic controls, IL6 is discharged into the bloodstream after muscle contraction increasing lipolysis and improving insulin resistance.
'Trans-signaling' in central nervous system also regulates energy and glucose homeostasis (By similarity).
IL6 mediates, through GLP-1, crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand (By similarity). It also acts as a myokine (Probable).
IL6 plays a protective role during liver injury, being required for maintenance of tissue regeneration (By similarity). It also has a pivotal role in iron metabolism by regulating HAMP/hepcidin expression upon inflammation or bacterial infection.
Through activation of IL6ST-YAP-NOTCH pathway, IL6 induces inflammation-induced epithelial regeneration (By similarity).
Pathways
There are 74 pathways. Here are some of them.
14-3-3 Induced Intracellular Signaling
Actin-Based Motility by Rho Family GTPases
Activation of cAMP-Dependent PKA
Activation of PKA through GPCR
Activation of PKC through GPCR
Akt Signaling
all-trans-Retinoic Acid Mediated Apoptosis
all-trans-Retinoic Acid Signaling in Brain
Antioxidant Action of Vitamin-C
Apoptotic Pathways in Synovial Fibroblasts
Breast Cancer Regulation by Stathmin1
cAMP Pathway
Cellular Apoptosis Pathway
Colorectal Cancer Metastasis
CREB Pathway
Cytokine Network
DHA Signaling
eIF2 Pathway
Endothelin-1 Signaling Pathway
Drugs
About FGF2, there are 101 pipelines under study, 36 of which have been approved.
Siltuximab is an interleukin antagonist used to treat multicentric Castleman's disease (MCD) in patients who are HIV and HHV-8 negative.
Adalimumab is a monoclonal anti-tumor necrosis factor alpha antibody used in the treatment of a wide variety of inflammatory conditions such as rheumatoid arthritis, Crohn's disease, and ankylosing spondylitis.
Etanercept is a protein therapy based on the binding fragment of the tumour necrosis factor alpha receptor used to treat severe rheumatoid arthritis and moderate to severe plaque psoriasis.
Fenofibrate is a peroxisome proliferator receptor alpha activator used to lower LDL-C, total-C, triglycerides, and Apo B, while increasing HDL-C in hypercholesterolemia, dyslipidemia, and hypertriglyceridemia.
Infliximab is a monoclonal anti tumor necrosis factor alpha antibody used in the treatment of a wide variety of inflammatory conditions such as rheumatoid arthritis, Crohn's disease, and ankylosing spondylitis.
Iron sucrose is an compound used as a source of iron in patients with iron deficiency anemia associated with chronic kidney disease (CKD).
Ribavirin is a guanosine nucleoside used to treat some forms of Hepatitis C.
Rituximab is a monoclonal anti-CD20 antibody used to treat non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Wegener's granulomatosis, pemphigus vulgaris, and rheumatoid arthritis.
Simvastatin is an HMG-CoA reductase inhibitor used to lower lipid levels and reduce the risk of cardiovascular events including myocardial infarction and stroke.