Interleukin 6 (IL-6) is a multifunctional cytokine that modulates immune responses, acute phase reactions, and hematopoiesis and plays a central role in host defense mechanisms. The human IL-6 gene has been identified on chromosome 7. IL-6 is not usually produced continuously by normal cells, but its expression is easily induced by a variety of cytokines, lipopolysaccharides (LPS), and viral infections. The IL-6 gene product is a unique protein chain with a molecular weight ranging from 21 to 28 kDa, depending on the cell type. Responsible for this heterogeneity appears to be extensive post-translational modifications such as N- and O-glycosylation as well as phosphorylation.
Interleukin 6 is produced by a variety of cells. IL-6-producing cells include CD8+ T cells, fibroblasts, adipocytes, osteoblasts, megakaryocytes, endothelial cells (under the influence of endothelins), sympathetic neurons, cerebral neurons of the cortex, adrenal medulla cells, retinal cells, histiocytes, keratinocytes, Langerhans cells, astrocytes, neutrophils, monocytes, eosinophils, colorectal epithelial cells, B lymphocytes and beta cells of the pancreatic islets. It acts in a wide range of tissues, promoting growth, inhibition, and differentiation, depending on the nature of the target cells. IL-6 induces signaling through a heterodimeric cell surface receptor consisting of a binding subunit (IL-6 Ra) and a signal transduction subunit (gp130). The gp130 subunit is found in many cell types, whereas the IL-6 Ra subunit is mainly restricted to hepatocytes, monocytes, and non-stimulated lymphocytes.
Interleukin 6 in combination with TNF-α and IL-1 elicits an acute inflammatory response. IL-6 is almost solely responsible for fever and the acute phase response in the liver and is an important factor in the transition from acute inflammation to acquired immunity or to chronic inflammatory disease. When deregulated, it contributes to chronic inflammation in conditions such as obesity, insulin resistance, inflammatory bowel diseases, arthritis, and septicemia. IL-6 regulates bone resorption and is an important factor in inflammatory joint damage in rheumatoid arthritis, by promoting Th17 cell growth and action. It also contributes to the development of atherosclerotic plaque and its destabilization as well as to the development of carcinogenesis associated with inflammation. IL-6 can also function as an anti-inflammatory molecule, as it does in skeletal muscle where it is secreted in response to exercise. In addition, it enhances the proliferation of hematopoietic stem cells and the differentiation of memory B cells and plasma cells.
Interleukin 6 participates in:
- Induction of B-cell differentiation
- Induction of acute-phase proteins in liver cells
- Promoting growth in myeloma / plasmacytoma / hybridoma cells
- Induction of IL-2 and IL-2 receptor expression
- T-cell proliferation and differentiation
- Inhibition of cellular growth of some myeloid leukemia cell lines and induction of their differentiation into macrophages
- Enhancement of IL-3-mediated multipotent stem cell formation of hematopoietic stem cells and induction of megakaryocyte maturation as a thrombogenic factor
- Induction of mesangial cell growth
- Induction of differentiation of neural PC12 cells
- Stimulation of keratinocyte growth
The abnormal production of IL-6 was the first cytokine proposed as the causative agent for polyclonal B-cell activation and production of autoantibodies in patients with cardiac myxoma. Since then, IL-6 has been suggested to be involved in the pathogenesis of a variety of diseases.
Measurement of interleukin 6 levels in serum and other biological fluids provides detailed knowledge of various pathological conditions.
Infections. The biological fluids of patients with acute local bacterial or viral infections and the serum of patients with bacteriemia from Gram-negative or positive microorganisms contain elevated levels of biologically active IL-6.
Gynecological infections. IL-6 has been reported as an important marker for intraamniotic infections.
Diseases related to changes in the immune system (B-cell polyclonal abnormalities or autoimmune diseases). Elevated levels of circulating IL-6 have been detected in patients with heart myxoma, Castleman's disease, rheumatoid arthritis, IgM gammopathies, in patients with acquired immunodeficiency syndrome as well as in alcoholic cirrhosis of the liver.
Proliferative diseases. Elevated plasma IL-6 levels have been observed in patients with psoriasis and with mesangial proliferative glomerulonephritis.
Neoplastic diseases. Elevated levels of IL-6 in the systemic circulation have been detected in patients with multiple myeloma and other B-cell malignancies, in Lennert T lymphoma, in Castleman's disease, in renal cell carcinoma, and in various other solid tumors.
Inflammatory reactions. IL-6 is involved in the induction of acute-phase proteins and fever. Elevated serum IL-6 levels are also found in patients with severe burns and in patients with postoperative complications, in serum and urine of transplant recipients before transplant rejection, in patients with septic shock, and in patients with inflammatory and traumatic arthritis.
Important Note
Laboratory test results are the most important parameter for the diagnosis and monitoring of all pathological conditions. 70%-80% of diagnostic decisions are based on laboratory tests. The correct interpretation of laboratory results allows a doctor to distinguish "healthy" from "diseased".
Laboratory test results should not be interpreted from the numerical result of a single analysis. Test results should be interpreted in relation to each individual case and family history, clinical findings, and the results of other laboratory tests and information. Your personal physician should explain the importance of your test results.
At Diagnostiki Athinon we answer any questions you may have about the test you perform in our laboratory and we contact your doctor to get the best possible medical care.
