Interleukin-6: discovery of a pleiotropic cytokine - PubMed (original) (raw)

Review

. 2006;8 Suppl 2(Suppl 2):S2.

doi: 10.1186/ar1916. Epub 2006 Jul 28.

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Review

Interleukin-6: discovery of a pleiotropic cytokine

Tadamitsu Kishimoto. Arthritis Res Ther. 2006.

Abstract

In the late 1960s, the essential role played by T cells in antibody production was reported. This led to our hypothesis that certain molecules would have to be released from T cells to effect the stimulation of B cells. This hypothesis was shown to be true. There were certain factors present in the culture supernatant of T cells that induced proliferation and differentiation of B cells. The factor that induced B cells to produce immunoglobulins was initially named B cell stimulatory factor-2. The cDNA encoding the human B cell stimulatory factor-2 was cloned in 1986. At the same time, IFN-beta2 and a 26 kDa protein in the fibroblasts were independently cloned and found to be identical to B cell stimulatory factor-2. Later, a hybridoma/plasmacytoma growth factor and a hepatocyte stimulating factor were also proven to be the same molecule as B cell stimulatory factor-2. Various names were used for this single molecule because of its multiple biological activities, but these have all been unified and the molecule is now known as IL-6. Since the discovery of IL-6, rapid progress has been made in our understanding of IL-6 activities, the IL-6 receptor system and the IL-6 signal transduction mechanism. More importantly, it has been shown to be involved in a number of diseases such as rheumatoid arthritis and Castleman's disease. When taking into account all the accumulated basic research on the various aspects of this molecule, it appeared that blocking the activity of IL-6 was a feasible, new therapeutic approach for chronic inflammatory diseases.

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Figures

Figure 1

Figure 1

Feedback regulation in IL-6 signaling by SOCS. IL, interleukin; IL-6R, interleukin-6 receptor; JAK, Janus activated kinase; SOCS, suppressors of cytokine signaling; STAT, signal transducer and activator of transcription.

Figure 2

Figure 2

Blockade of IL-6 signals by anti-IL-6 receptor antibody (MRA, Tocilizumab). h, human; IL, interleukin; sIL-6R, soluble interleukin-6 receptor.

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References

    1. Miller JF, Mitchell GF. Cell to cell interaction in the immune response. I. Hemolysin-forming cells in neonatally thymectomized mice reconstituted with thymus or thoracic duct lymphocytes. J Exp Med. 1968;128:801–820. doi: 10.1084/jem.128.4.801. - DOI - PMC - PubMed
    1. Claman HN, Chaperon EA, Selner JC. Thymusmarrow immunocompetence. 3. The requirement for living thymus cells. Proc Soc Exp Biol Med. 1968;127:462–466. - PubMed
    1. Hirano T, Matsuda T, Hosoi K, Okano A, Matsui H, Kishimoto T. Absence of antiviral activity in recombinant B cell stimulatory factor 2 (BSF-2) Immunol Lett. 1988;17:41–45. doi: 10.1016/0165-2478(88)90099-5. - DOI - PubMed
    1. Suematsu S, Matsusaka T, Matsuda T, Ohno S, Miyazaki J, Yamamura K, Hirano T, Kishimoto T. Generation of plasmacytomas with the chromosomal translocation t(12;15) in interleukin 6 transgenic mice. Proc Natl Acad Sci USA. 1992;89:232–235. doi: 10.1073/pnas.89.1.232. - DOI - PMC - PubMed
    1. Kawano M, Hirano T, Matsuda T, Taga T, Horii Y, Iwato K, Asaoku H, Tang B, Tanabe O, Tanaka H. et al.Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature. 1988;332:83–85. doi: 10.1038/332083a0. - DOI - PubMed

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