IL-6 in Inflammation, Immunity, and Disease

Overview

Journal Cold Spring Harb Perspect Biol

Specialties Biology
Molecular Biology

Date 2014 Sep 6

PMID 25190079

Citations 1940

Authors

Toshio Tanaka

Masashi Narazaki

Tadamitsu Kishimoto

Affiliations

Soon will be listed here.

Abstract

Interleukin 6 (IL-6), promptly and transiently produced in response to infections and tissue injuries, contributes to host defense through the stimulation of acute phase responses, hematopoiesis, and immune reactions. Although its expression is strictly controlled by transcriptional and posttranscriptional mechanisms, dysregulated continual synthesis of IL-6 plays a pathological effect on chronic inflammation and autoimmunity. For this reason, tocilizumab, a humanized anti-IL-6 receptor antibody was developed. Various clinical trials have since shown the exceptional efficacy of tocilizumab, which resulted in its approval for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. Moreover, tocilizumab is expected to be effective for other intractable immune-mediated diseases. In this context, the mechanism for the continual synthesis of IL-6 needs to be elucidated to facilitate the development of more specific therapeutic approaches and analysis of the pathogenesis of specific diseases.

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References

Scala G, Ruocco M, Ambrosino C, Mallardo M, Giordano V, Baldassarre F . The expression of the interleukin 6 gene is induced by the human immunodeficiency virus 1 TAT protein. J Exp Med. 1994; 179(3):961-71. PMC: 2191426. DOI: 10.1084/jem.179.3.961. View

Okada M, Kitahara M, Kishimoto S, Matsuda T, Hirano T, Kishimoto T . IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T cells. J Immunol. 1988; 141(5):1543-9. View

Palanisamy V, Jakymiw A, Van Tubergen E, DSilva N, Kirkwood K . Control of cytokine mRNA expression by RNA-binding proteins and microRNAs. J Dent Res. 2012; 91(7):651-8. PMC: 3383846. DOI: 10.1177/0022034512437372. View

Okiyama N, Sugihara T, Iwakura Y, Yokozeki H, Miyasaka N, Kohsaka H . Therapeutic effects of interleukin-6 blockade in a murine model of polymyositis that does not require interleukin-17A. Arthritis Rheum. 2009; 60(8):2505-12. DOI: 10.1002/art.24689. View

Kishimoto T, Ishizaka K . Regulation of antibody response in vitro. VII. Enhancing soluble factors for IgG and IgE antibody response. J Immunol. 1973; 111(4):1194-205. View

Dragan Y, Schrenk D . Animal studies addressing the carcinogenicity of TCDD (or related compounds) with an emphasis on tumour promotion. Food Addit Contam. 2000; 17(4):289-302. DOI: 10.1080/026520300283360. View

Terpos E, Fragiadaki K, Konsta M, Bratengeier C, Papatheodorou A, Sfikakis P . Early effects of IL-6 receptor inhibition on bone homeostasis: a pilot study in women with rheumatoid arthritis. Clin Exp Rheumatol. 2011; 29(6):921-5. View

Puga A, Tomlinson C, Xia Y . Ah receptor signals cross-talk with multiple developmental pathways. Biochem Pharmacol. 2005; 69(2):199-207. DOI: 10.1016/j.bcp.2004.06.043. View

Hirano T, Matsuda T, Turner M, Miyasaka N, Buchan G, Tang B . Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis. Eur J Immunol. 1988; 18(11):1797-801. DOI: 10.1002/eji.1830181122. View

10.

Bettelli E, Carrier Y, Gao W, Korn T, Strom T, Oukka M . Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006; 441(7090):235-8. DOI: 10.1038/nature04753. View

11.

Nguyen N, Kimura A, Nakahama T, Chinen I, Masuda K, Nohara K . Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism. Proc Natl Acad Sci U S A. 2010; 107(46):19961-6. PMC: 2993339. DOI: 10.1073/pnas.1014465107. View

12.

Imai Y, Kuba K, Neely G, Yaghubian-Malhami R, Perkmann T, van Loo G . Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell. 2008; 133(2):235-49. PMC: 7112336. DOI: 10.1016/j.cell.2008.02.043. View

13.

Kumar H, Kawai T, Akira S . Pathogen recognition by the innate immune system. Int Rev Immunol. 2011; 30(1):16-34. DOI: 10.3109/08830185.2010.529976. View

14.

Nishimoto N, Yoshizaki K, Tagoh H, Monden M, Kishimoto S, Hirano T . Elevation of serum interleukin 6 prior to acute phase proteins on the inflammation by surgical operation. Clin Immunol Immunopathol. 1989; 50(3):399-401. DOI: 10.1016/0090-1229(89)90147-5. View

15.

Tanaka T . Can IL-6 blockade rectify imbalance between Tregs and Th17 cells?. Immunotherapy. 2013; 5(7):695-7. DOI: 10.2217/imt.13.47. View

16.

Bell D, Poland A . Binding of aryl hydrocarbon receptor (AhR) to AhR-interacting protein. The role of hsp90. J Biol Chem. 2000; 275(46):36407-14. DOI: 10.1074/jbc.M004236200. View

17.

Sandborg C, Mellins E . A new era in the treatment of systemic juvenile idiopathic arthritis. N Engl J Med. 2012; 367(25):2439-40. DOI: 10.1056/NEJMe1212640. View

18.

Burbach K, Poland A, Bradfield C . Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcription factor. Proc Natl Acad Sci U S A. 1992; 89(17):8185-9. PMC: 49882. DOI: 10.1073/pnas.89.17.8185. View

19.

Matsusaka T, Fujikawa K, Nishio Y, Mukaida N, Matsushima K, Kishimoto T . Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8. Proc Natl Acad Sci U S A. 1993; 90(21):10193-7. PMC: 47740. DOI: 10.1073/pnas.90.21.10193. View

20.

Heinrich P, Castell J, Andus T . Interleukin-6 and the acute phase response. Biochem J. 1990; 265(3):621-36. PMC: 1133681. DOI: 10.1042/bj2650621. View