Interleukin-6 (IL-6)

Interleukin 6 (IL6), also referred to as B-cell stimulatory factor-2 (BSF-2) and interferon beta-2, is a cytokine involved in a wide variety of biological functions.

The cytokine Interleukin-6 has multiple functions in cell growth, hematopoiesis, bone metabolism, immune cell activation, and inflammation.

It has an essential role in the final differentiation of B cells into immunoglobulin-secreting cells, as well as inducing myeloma/plasmacytoma growth, nerve cell differentiation, and, in hepatocytes, acute-phase reactants.

A number of other cytokines may be grouped with IL6 on the basis of sequence similarity.

These include granulocyte colony-stimulating factor (GCSF) and myelomonocytic growth factor (MGF).

GCSF acts in hematopoiesis by affecting the production, differentiation, and function of 2 related white cell groups in the blood.

MGF also acts in hematopoiesis, stimulating proliferation and colony formation of normal and transformed avian cells of the myeloid lineage.

Cytokines of the IL6/GCSF/MGF family are glycoproteins of about 170 to 180 amino acid residues that contain four conserved cysteine residues involved in two disulphide bonds.

IL-6 has 3 antigenic sites: one, two, and three.

Augments cell growth, inhibits apoptosis, and enhances drug resistance in multiple myeloma.

Elevated in tissues undergoing angiogenesis.

Functions as either a pro- or anti-inflammatory cytokine depending on underlying stimulus.

IL-6 is a pleiotropic cytokine that is produced by a large number of cell types and is involved in a variety of inflammatory processes.  

In response to tissue injury it is pro-inflammatory.

It is a key mediator in chronic inflammation.

IL6 signaling is conveyed through the IL-6/IL-6R complex, and two molecules of the single transducer gp130.

Soluble IL-6R originates from proteolytic, cleavage of membrane-bound, IL-6R, and can form IL-6/sIL-6R complexes that convey IL-6 trans signaling.

IL-6 trans signaling is primarily responsible for chronic inflammation.

IL-6 is pro-inflammatory in nature and can be produced by many cells of the immune system as well as non-immune cells, like fibroblasts.

IL-6 is considered the primary mediator of CRS (cytokine release syndrome).

IL-6 normally binds to membrane-bound IL-6receptor on certain immune effector cells and has anti-inflammatory properties. 

When IL-6 levels are increased in CRS, it may bind to a soluble form of IL-6 inducing a pro inflammatory response by activation of a trans signaling pathway. 

This cytokine has been identified in many organs such as the lungs, adipose tissue, muscle, and brain. 

The concentration of IL-6 cytokine is usually very low or non-detectable in young adults though levels increase in old age and are very high in the elderly.

Interleukin-6 stimulates chemokine production and favors the transition from acute to chronic inflammation, is a potent inducer of the production of acute-phase proteins in the liver through reprogramming and reorientation of metabolic functions by decreasing albumin production and increased production of acute-phase proteins.

Moreover, elevated IL-6 has also been associated with disability and mortality in older adults. 

High serum levels are associated with cognitive impairment, low locomotion, and depression.

Local tissue injury involves production of cytokines at the site of inflammation.

IL-6 induces angiogenesis by stimulating VEGF, a mitogen for endothelial cells.

Elevated in the CSF of patients with neuromyelitis opticum spectrum disorder (NMOSD).

Patients with NMO and NMOSD have elevated levels of IL-6 in cerebro-spinal fluid and serum during periods of active disease.



Some of the pro-inflammatory processes involved in NMOSD are thought to involve IL-6, including the formation of pathological autoantibodies against aquaporin-4 (AQP4), and the permeability of the blood-brain barrier to mediators of inflammation.


Promotes the differentiation of naIve T cells into pro inflammatory type 17 helper T cells which, along with interleukin-6 promote the differentiation of B cells into AQP4-IgG producing plasmablasts.

Elevated in serum and pleural effusions of patients with mesothelioma and correlated with thrombocytosis in such patients.

A cytokine responsible for chronic inflammation associated with rheumatoid arthritis in joints and systemically.

One of the most abundant cytokines in the serum and synovial fluid of inflamed joints of patients with rheumatoid arthritis.

Is associated with disease activity and articulate destruction in TA.

Activates pro inflammatory cells and mediators within the joint such as neutrophils, macrophages, fibroblast-like synoviocytes ,T cells and B cells.

Degrades cartilage by activating fibroblast-like synoviocytes and chondrocytes to release cathepsins and matrix metalloproteinases in rheumatoid arthritis.

Stimulates osteoclastogenesis and osteoclast activity, leading to structural damage through bone resorption in’rheumatoid arthritis.

The most abundant proinflammatory cytokine in the rheumatoid synovium and a major influence of an autoimmune response.

Has the ability to bind to soluble receptors and membranes.

When unregulated can stimulate and maintain chronic inflammation in articular and extraarticular sites in rheumatoid arthritis.

Contributes to synovial proliferation and destruction of cartilage and bone in inflamed joints.

Interaction with IL-6 and other cytokines, immune cells, synovial fibroblasts and osteoclasts associated with signs and symptoms of rheumatoid arthritis including, cartilage destruction, bone degradation and pannus formation.

IL-6 found in abundance in rheumatoid synovium and markedly elevated in the serum of patients rheumatoid arthritis.

IL-6 levels correlate with rheumatoid disease stage, severity of joint destruction and many systemic manifestations of RA.

Can disrupt iron homeostasis resulting in anemia, as is seen in rheumatoid arthritis.

IL-6 levels may activate osteoclasts and accelerated osteoporosis.

Associated with fever, pain, cognitive impairment, insomnia and anorexia.

IL-6 levels predict distant breast cancer recurrence.


The inflammatory cytokine interleukin 6 may be a biomarker for distant recurrence of breast cancer among patients treated for stage II-III HER2-negative disease.


In a case-control study of 498 women with breast cancer treated with surgery and adjuvant chemotherapy, as well as endocrine therapy for women with estrogen receptor (ER)�positive tumors, those with higher serum levels of IL-6 at diagnosis had a significantly greater risk for disease recurrence than women with lower levels of the cytokine, 


This analysis indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher distant recurrence risk in high-risk stage II-III breast cancer despite optimal adjuvant systemic therapy.



Systemic inflammation is suspected as a contributing factor to cancer progression and disease recurrence.

Induces hepcidin synthesis and can contribute disruption of iron homestasis.

Associated with hypothalamic-pituitary adrenal axis that contributes to fatigue in patients with rheumatoid arthritis.

Upregulates hepatic production of acute phase proteins such as CRP, SAA and fibrinogen, which have been associated with cardiovascular risk.

Elevated levels predictive of endothelial dysfunction and increased atherogenesis.

Associated with fatigue, pain and fever.

Elevated in several cancers, including hepatocellular carcinoma.

Estrogen inhibits the induction of IL-6 produced by Kupffer cells.

Satralizumab a subcutaneous administered humanized monoclonal antibody that binds to both membrane found in soluble interleukin-6 receptors and prevents the binding of interleukin-6, thus blocking interleukin-6-signaling pathways that are involved in inflammation.

((Tocilizumab)) is a IL-6 inhibitor.


In critically ill patients with Covid-19 patients on supportive therapy with Interleukin-six receptor antagonists tocilizumab and sarilumab improve outcomes, including survival.


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