Interleukins are a very important genetic group of cytokines. As of 2022, 40 members have been recognized; they play an important role in a series of processes such as the maturation, activation, proliferation and immune regulation of immune cells.In addition, interleukins are involved in a variety of physiological and pathological responses of the airframe.

Interleukin 6 (IL-6) is an important member of the cytokine network and is central in the acute inflammatory response. Discovered in 1980 by Weissenbach, interleukin 6 is a multifunctional cytokine with important roles in human metabolism, autoimmune cell differentiation, and disease treatment.

IL-6 structural properties

IL-6 is a small molecule peptide, consisting of four alpha-helices. It has a molecular weight of 19-28 KD, 184 hydrogenated acid residues, normally exists as a monomer, with an isoelectric point of 5.0, a glycosylation site and two disulfide bonds. The gene encoding IL-6 is on chromosome 7P15-21 and consists of four introns and five exons.

IL-6 synthesis pathway

IL-6 can be produced by almost all stromal and immune system cells, such as B lymphocytes, T lymphocytes, macrophages, monocytes, dendritic cells, mast cells and other non-lymphoid cells, such as fibroblasts, endothelial cells, keratin-forming cells, glomerular thylakoid cells and tumor cells.

The major activators of IL-6 expression are IL-1b and tumor necrosis factor (TNF-a), although IL-6 synthesis is also facilitated by other pathways such as Toll-like receptors, prostaglandins, adipokines, stress responses, and other cytokines.

The interleukin IL-6 is produced by monocytes and macrophages stimulated by Toll-like receptors in the early stages of infectious inflammation. It can also be produced by cells stimulated by Toll-like receptors in non-infectious inflammations, such as burns or traumatic injuries. This acute IL-6 expression plays a central role in host defense by stimulating various cell populations.

Various stimuli, such as ultraviolet light, radiation, reactive oxygen species, microorganisms, viruses, and other types of pro-inflammatory factors, can increase the synthesis of IL-6.

Interleukin 6 signaling pathway

There are 3 main pathways of IL-6 signaling, which are classical signaling, trans-signaling, and trans-presentation.

Classical Signaling

In the classical signaling pathway, IL-6 binds to its receptor IL-6R to form a complex, and then binds to the membrane protein gp130 to initiate intracellular signaling. IL-6R exists in both transmembrane and soluble forms. IL-6 binds to both forms and then interacts with gp130, triggering downstream signaling and gene expression.

Trans-Signaling

In the trans signaling pathway, IL-6R exists in a soluble form (sIL-6R). The binding affinity of sIL-6R to IL-6 is similar to that of IL-6R, and its binding complex binds to gp130, which in turn initiates intracellular signaling. In the classical signaling pathway, many cells cannot respond to IL-6 signals because they do not express IL-6R, but some of these cells can be stimulated by the complex of sIL-6R-IL-6 and respond to IL-6 signals, causing Cell Signaling.

Trans-Presentation

The trans-presentation signaling pathway was discovered in previous studies and mainly occurs in the antigen-specific interaction of dendritic cells that provide IL-6 signals and T cells that receive IL-6. After IL-6 binds to IL-6R in dendritic cells, it is transported to the plasma membrane, recognizes T cells and responds to gp130, phosphorylates STAT3 in T cells, and initiates the signal transduction process.

Interleukin 6 biological activity

IL-6 promotes T-cell population expansion and activation and B-cell differentiation, modulates acute-phase responses, and can affect hormone-like properties of vascular disease, lipid metabolism, insulin resistance, mitochondrial activity, neuroendocrine system, and neuropsychological behavior. In addition, IL-6 promotes differentiation of osteoclasts and angiogenesis, proliferation of keratinocytes and glomerular membrane cells, and growth of myeloma and plasmacytoma cells.

Effects on B lymphocytes: IL-6 can induce B cells to proliferate, differentiate and produce antibodies. When B cells are activated after being stimulated by antigens and differentiate into IgM, IgG, and ISA antibodies, IL-6 is especially required.

Effects on T lymphocytes: IL-6 is a terminal cofactor for cytotoxic T lymphocytes (CTL), which induces CTL activity and enables immature thymocytes to develop into CTL. IL-6 is also an activating factor of T cells, and can also induce T cells to express IL-2 receptors through the second messenger effect.

Effects on hepatocytes: IL-6 is a strong inducer of acute phase response proteins, which can induce hepatocytes to synthesize acute phase response proteins at the level of gene transcription, among which the increase in SAA and CRP is particularly evident.

Effects on hematopoietic stem cells: IL-6 can synergize with other cytokines to promote the growth of early bone marrow stem cells, enhance blood cell differentiation, and promote their colony formation.

Involvement in the development of immune abnormal diseases: Patients with hypergammaglobulinemia, cardiac mucinoma, bladder cancer, chronic rheumatoid arthritis, and other patients are accompanied by abnormally increased levels of IL-6.

Participate in the occurrence and development of cardiovascular diseases: myocardial ischemia, coronary atherosclerosis, angina pectoris, congestive heart failure, hypertension and other patients are accompanied by abnormally increased levels of IL-6.

IL-6 is a cytokine secreted by T cells, B cells, mononuclear macrophages, and endothelial cells after the body is stimulated by inflammation. Elevated IL-6 may have dual effects: on the one hand, as a signal to mobilize body defense, It can differentiate and down-regulate the pro-inflammatory response caused by tumor necrosis factor, etc., and can induce the apoptosis of polymorphonuclear leukocytes, so that the inflammatory response can disappear normally; on the other hand, it can lead to immune dysfunction and promote the production of macrophages. Transforming growth factor beta (TGF-β), and TGF-β is related to the suppression of immune function after injury.

IL-6 Clinical Applications

In the "Expert Consensus on Interpretation of Clinical Significance of Infection-related Biomarkers", it is pointed out:

In the inflammatory response, the increase of IL-6 is earlier than other cytokines, and also earlier than CRP and PCT, and it lasts for a long time, so it can be used to assist the early diagnosis of acute infection.

IL-6 can also be used to evaluate the severity of infection and judge prognosis when IL-6>1000ug/L indicates a poor prognosis.

Dynamic observation of IL-6 levels can also help understand the battle against infectious disease and response to treatment.

IL-6, CRP and PCT association

IL-6 is involved in the occurrence and development of many diseases, and its blood level is closely related to inflammation, viral infection, and autoimmune diseases, and its change is earlier than that of CRP and PCT. Compared with the three, the sensitivity of IL-6 is higher than that of PCT and CRP, but its specificity is worse than that of PCT, and PCT and CRP just make up for its deficiency.

IL-6 is an early warning indicator of SIRS/sepsis sensitivity; PCT peaks late and has a longer half-life, which is a specific diagnostic indicator for (bacterial infection) sepsis; CRP is an auxiliary diagnostic indicator. The combination of the three, continuous dynamic monitoring of high-risk groups of sepsis, is of great significance for early detection and early treatment.

ELK Biotechnology can provide the following kits for some IL6-related indicators: