L6，全稱為白細胞介素6，是一種由多種細胞產(chǎn)生的細胞因子，可通過多種途徑引發(fā)免疫反應(yīng)和炎癥反應(yīng)，其與多種疾病的發(fā)生和發(fā)展密切相關(guān)。最近的研究表明，IL6在新冠疫情中發(fā)揮了重要作用，其高水平與COVID-19的嚴重程度和病死率密切相關(guān)。IL6的抑制劑已被證明在COVID-19治療中有潛在的療效，并且正在進行進一步的臨床研究。

Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. 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, 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, is required for the differentiation of B cells into immunoglobulin-secreting cells. Plays a major role in the differentiation of CD4(+) T cell subsets. Essential factor for the development of T follicular helper (Tfh) cells that are required for the induction of germinal-center formation. Required to drive naive CD4(+) T cells to the Th17 lineage. Also required for proliferation of myeloma cells and the survival of plasmablast cells.; 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. Induces, through 'trans-signaling' and synergistically with IL1B and TNF, the production of VEGF. Involved in metabolic controls, 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. Mediates, through GLP-1, crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand. Also acts as a myokine (Probable). Plays a protective role during liver injury, being required for maintenance of tissue regeneration. 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, induces inflammation-induced epithelial regeneration.

1. Acute exercise in children with juvenile idiopathic arthritis induced slightly musculoskeletal leg pain and transient increased plasma calprotectin levels but not IL-6 levels PMID: 30008613
2. Genotype frequencies in the degenerative lumbar scoliosis patients and controls revealed a significant difference for the IL6-572 G/C polymorphism. A significant association was found between the IL6-572 G/C polymorphism and measured bone mineral densities at the lumbar spine. PMID: 28378072
3. In glioblastoma, colony-stimulating factor-1 and angiocrine IL-6 induce robust arginase-1 expression and macrophage alternative activation, mediated through peroxisome proliferator-activated receptor-gamma-dependent transcriptional activation of hypoxia-inducible factor-2alpha. PMID: 29422647
4. study demonstrated novel molecular events for leptin-induced inflammation in ligamentum flavum (LF) tissue by promoting IL-6 expression and thus might have potential implications for clarifying the mechanism underlying LF fibrosis and hypertrophy. PMID: 29436483
5. The objective of this study was to evaluate the diagnostic value of serum and synovial fluid interleukin (IL)-6 levels for Periprosthetic Joint Infection. PMID: 28473693
6. The elevated levels of both serum Shh and IL-6 were mainly observed in BC patients who had a significantly higher risk of early recurrence and bone metastasis, and associated with a worse survival for patients with progressive metastatic BC. PMID: 28496132
7. study suggests that-174 G/C polymorphism of IL-6 gene differs in athletes, G allele and GG genotype is higher than the other ones, at least in Turkish athletes, and therefore should be taken into consideration when determining genetic aspects of athletes. PMID: 30213294
8. studies reveal that IL-6 action in T cells through classical IL-6 signalling promotes inflammation and insulin resistance early during obesity development, which can be compensated for by enhanced IL-6 trans-signalling at later stages PMID: 28466852
9. IL-6 signalling in primary human macrophages increased intracellular Bacillus Calmette-Guerin (BCG) and Mycobacterium tuberculosis numbers in a dose-dependent manner promoting mycobacterial survival and BCG-induced lipid accumulation. PMID: 28262681
10. The analysis of the effect of the individual SNPs(PON1, IL-6, ITGB3, and ALDH2 ) and GRS groups on different lipid profile parameters revealed no significant association of any of the tested SNPs with any lipid parameter, however, the GRS groups showed marginally significant for TC and highly significant association for TG, LDL-c and HDL-c PMID: 30261890
11. Our results showed that IL-37 plays an inhibitory role in non-small cell lung cancer progression, possibly by suppressing STAT3 activation and decreasing epithelial-to-mesenchymal transition by inhibiting IL-6 expression. IL-37 could serve as a potential novel tumor suppressor in non-small cell lung cancer PMID: 29575809
12. Although interleukin-6 (IL-6) mRNA level was higher in 3D-culured cells, its secretion levels were higher in 2D-cultured cells. In addition, the levels of mRNA and protein expression of regnase-1, regulatory RNase of inflammatory cytokine, significantly increased in 3D culture, suggesting post-translational modification of IL-6 mRNA via regnase-1. PMID: 30096769
13. indicate that the distribution of IL6-174G/C (rs1800795) SNP was marginally associated with multiple sclerosis susceptibility PMID: 30069682
14. FABP5 promotes tumor angiogenesis via activation of the IL6/STAT3/VEGFA signaling pathway in hepatocellular carcinoma. PMID: 29957468
15. Authors found that the IL-6 serum level was significantly higher in the SIRS group than in the control group. A significant association was observed in the genotypic distribution of the IL-6 - 572G allele in the SIRS group, when compared with the control group, and SIRS is more likely to occur in wasp sting patients with more than 10 stings. PMID: 30265566
16. adipocytes are capable of enhancing IL-6 production by CD4(+) T cells PMID: 29283192
17. Studied association of levels of IL-6 (interleukin-6) and TGF-beta in the pathogenesis of idiopathic epistaxis. PMID: 29893909
18. LL was significantly negatively correlated with PGC-1alpha, TNF-alpha, and IL-6 mRNA expressions. PGC-1alpha mRNA expression levels in paraspinal muscles may be affected by lumbar kyphosis. PMID: 30233161
19. Study found that IL-6 and IL-8 are necessary and sufficient to increase tumor cell migration in a cell density dependent manner with negligible feedback on cell proliferation. This effect is specific to metastatic cancer cells; IL-6 and IL-8 have no effect on the migration of normal and non-metastatic cancer cells. PMID: 28548090
20. Rheumatoid arthritis patients who had the best response to tocilimuzab had the highest levels of IL6 and the lowest levels of soluble IL6 receptor. PMID: 29157669
21. High IL6 expression is associated with retinopathy of prematurity. PMID: 29274846
22. Adult serum IL-6 levels were predicted across periods as long as 15 years by adolescents' inability to defuse peer aggression and poor peer-rated conflict resolution skills, and by independently observed romantic partner hostility in late adolescence. PMID: 29212559
23. Lysophosphatidylcholine induces COX-2-mediated IL-6 expression. NADPH oxidase/Reactive Oxygen Species is involved in Lysophosphatidylcholine-induced COX-2 expression. PMID: 30229288
24. The expression of IL-6 gene and protein was significantly induced by IL-17F. IL-17F activated TAK1 and NF-kappaB in airway smooth muscle cells. PMID: 28474507
25. IL-6 was over-expressed in SF from OA patients compared with normal donors. DNA hypomethylation and histone hyperacetylation were observed in the IL-6 promoter region in OA SF compared with normal SF. No differences in the status of H3K9 di-methylation, H3K27 tri-methylation and H3K4 tri-methylation in the IL-6 promoter region were observed between normal and OA SF. PMID: 28262826
26. Increased serum IL6 concentrations are associated with obstructive sleep apnea and glycemic status. PMID: 29305826
27. Study showed that activation of NF-kappaB/IL-6 is involved in moderate hyperthermia treatment induced progression of hepatocellular carcinoma cells. PMID: 29894725
28. the polymorphism rs1800795 is associated with serum IL-6 level and level of neuroblastoma risk; GG genotype might indicate that the tumor is highly malignant (prone to metastasis) and associated with poor prognosis PMID: 29692379
29. Findings indicate that childhood infections do not have an independent, lasting effect on circulating inflammatory marker levels subsequently in childhood; however, elevated inflammatory markers may be harmful for intellectual development/function. PMID: 29198208
30. This study found that the protein and mRNA expression levels of the IL-6 is significantly increased. PMID: 28476335
31. IL-6 may be used as a tumor marker for cancer diagnosis. It may be a clinically significant predictor and may represent a target for cancer treatment. However, to definitely conclude this, further extensive studies would be required PMID: 30249899
32. The findings suggest that male factor infertility might be associated with an increased level of interleukin-6. PMID: 28523952
33. Individuals with posttraumatic stress disorder showed a significant increase in the serum levels of IL-6 (and IL-10). PMID: 29179015
34. Data suggest that, in children with pediatric obesity, lifestyle weight-loss intervention results in down-regulation of serum cardiotrophin-1 (CTF1), interleukin-6 (IL6), and tumor necrosis factor-alpha (TNFA); expression of CTF1, IL6, and TNFA is also down-regulated in peripheral blood mononuclear cells after improvement in adiposity, body mass index, and waist-hip ratio. PMID: 28749076
35. Findings outlined in the current study demonstrated that the inhibition of P16 decreased the growth and metastasis potential of BC cells by inhibiting IL-6/JAK2/STAT3 signaling. PMID: 29388151
36. The G/C genotype and the minor allele C of the IL-6 rs1800795 SNP were more common in individuals with Type 2 Diabetes Mellitus than controls (p = 0.004, odds ratio [OR] = 1.98, 95% confidence interval [CI]: 1.24-3.18 and p = 0.011, OR = 1.59, 95% CI: 1.11-2.26, respectively). PMID: 29957071
37. The C allele of rs1800795 within IL-6 gene promoter, rs1800795-tobacco smoking and rs1800795-alcohol drinking interaction were all associated with increased CAD risk. PMID: 29889576
38. study emphasizes the importance of -572G > C polymorphism in increasing IL-6 levels, thereby showing its significant role in DVT in India. PMID: 29890913
39. Interleukin-6 Single Nucleotide Polymorphism is associated with Prostate Adenocarcinoma and Bone Metastasis. PMID: 29938471
40. In a multi-ethnic population with nonalcoholic fatty liver disease, IL-6 is independently associated with the prevalence and severity of subclinical coronary atherosclerosis. PMID: 29579601
41. in the patients with primary depression, depressive symptoms were associated with IL-6 PMID: 30148175
42. eNOS knockdown greatly enhanced endothelial IL-6 production and permeability in response to LPS. Knockdown of eNOS enhanced LPS-induced p38. Inhibition of p38 with SB203580 prevented IL-6 production, without altering permeability PMID: 29061842
43. The expression of the inflammatory cytokines interleukin (IL)6 and IL8 was significantly increased in endometriotic and cocultured cells compared with healthy ECs. PMID: 29901132
44. Leptin-to-adiponectin ratio and IL-6 were elevated in men with prostate cancer. Leptin, chemerin and IL-6 were associated with Gleason score. The relationships between leptin, chemerin and IL-6 were dependent on each other. PMID: 29465157
45. Collective evidence is supportive of the idea that IL-6 is an important participant during the EMT process in human intrahepatic biliary epithelial cells (HIBECs), as IL-6 stimulation can enhance the migration abilities of HIBEC, promote HIBEC cellular senescence and inhibit apoptosis of HIBECs, resulting in the EMT transformation of HIBECs. PMID: 28857276
46. Our findings suggest that IL-6-mediated cross-talk between preadipocytes and breast DCIS cells can promote the progression of early stage breast cancer. PMID: 30134951
47. Our study suggests the second day as the golden time for measuring the serum levels of IL-6. These findings warn us to take more health care actions in patients with higher serum levels of IL-6 on the second day. PMID: 29947344
48. A small drug acting as a JAK1/2 inhibitor may also counteract the repressing effects of IL-6. PMID: 29162613
49. addition of colivelin, a STAT3 activator, instead of IL-6 and C2C12 conditioned medium, promoted the myogenic differentiation of adipose tissue-derived stem cells. PMID: 29882916
50. IL-6 G allele promoter increased stroke recurrent risk, therefore, it would be a predictor for recurrence of stroke in the young with moderate internal carotid artery stenosis. PMID: 29091301

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Rheumatoid arthritis systemic juvenile (RASJ)

Secreted.

IL-6 superfamily

Produced by skeletal muscle.

HGNC: 6018

OMIM: 147620

KEGG: hsa:3569

STRING: 9606.ENSP00000258743

UniGene: Hs.654458