Limits...
Interleukin 6 in autoimmune and inflammatory diseases: a personal memoir.

Hirano T - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2010)

Bottom Line: Characterization of IL-6 revealed a multifunctional cytokine that is involved in not only immune responses but also hematopoiesis, inflammation, and bone metabolism.F759 arthritis is dependent on CD4(+) T cells, IL-6, and IL-17A, and is enhanced by the pX gene product from human T cell leukemia virus 1 (HTLV-1).Furthermore, this interaction is mediated by the IL-6 amplifier through STAT3 and NF-kappaB.

View Article: PubMed Central - PubMed

Affiliation: JST-CREST, WPI Immunology Frontier Research Center, Osaka University, Japan. hirano@molonc.med.osaka-u.ac.jp

ABSTRACT
In this review, the author discusses the research that led to the identification and characterization of interleukin 6 (IL-6), including his own experience isolating IL-6, and the roles this cytokine has on autoimmune and inflammatory diseases. The cDNAs encoding B-cell stimulatory factor 2 (BSF-2), interferon (IFN)-beta2 and a 26-kDa protein were independently cloned in 1986, which in turn led to the identification of each. To resolve the confusing nomenclature, these identical molecules were named IL-6. Characterization of IL-6 revealed a multifunctional cytokine that is involved in not only immune responses but also hematopoiesis, inflammation, and bone metabolism. Moreover, IL-6 makes significant contributions to such autoimmune and inflammatory diseases as rheumatoid arthritis (RA).IL-6 activates both the STAT3 and SHP2/Gab/MAPK signaling pathways via the gp130 signal transducer. F759 mice, which contain a single amino-acid substitution in gp130 (Y759F) and show enhanced STAT3 activation, spontaneously develop a RA-like arthritis as they age. F759 arthritis is dependent on CD4(+) T cells, IL-6, and IL-17A, and is enhanced by the pX gene product from human T cell leukemia virus 1 (HTLV-1). Arthritis development in these mice requires that the F759 mutation is present in nonhematopoietic cells, but not in immune cells, highlighting the important role of the interaction between nonimmune tissues and the immune system in this disease. Furthermore, this interaction is mediated by the IL-6 amplifier through STAT3 and NF-kappaB. Ultimately, this model may represent a general etiologic process underlying other autoimmune and inflammatory diseases. More importantly, the understanding of IL-6 has paved the way for new therapeutic approaches for RA and other autoimmune and inflammatory diseases.

Show MeSH

Related in: MedlinePlus

Multifunctional cytokine IL-6 is produced by a variety of cell types, including T cells, B cells, macrophages, astrocytes, stromal cells, vascular endothelial cells, smooth muscle cells, and fibroblasts. IL-6 induces antibody expression (B cell stimulatory factor 2) and cytotoxic T-lymphocyte activity (T cell activation factor). IL-6 was also referred to as a hybridoma/plasmacytoma growth factor and a hepatocyte stimulatory factor. IL-6 acts as a growth factor for AIDS-related Kaposi’s sarcoma, mesangial cells, and renal cell carcinomas, and as a thrombopoietin, a nerve growth factor, a hormone-inducing factor in the pituitary gland, an osteoclast-inducing factor, and a keratinocyte growth factor.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3066534&req=5

fig03: Multifunctional cytokine IL-6 is produced by a variety of cell types, including T cells, B cells, macrophages, astrocytes, stromal cells, vascular endothelial cells, smooth muscle cells, and fibroblasts. IL-6 induces antibody expression (B cell stimulatory factor 2) and cytotoxic T-lymphocyte activity (T cell activation factor). IL-6 was also referred to as a hybridoma/plasmacytoma growth factor and a hepatocyte stimulatory factor. IL-6 acts as a growth factor for AIDS-related Kaposi’s sarcoma, mesangial cells, and renal cell carcinomas, and as a thrombopoietin, a nerve growth factor, a hormone-inducing factor in the pituitary gland, an osteoclast-inducing factor, and a keratinocyte growth factor.

Mentions: I had wished to isolate the factor that stimulates B cells to produce immunoglobulin. Once we cloned the factor, however, it was clear that IL-6 acts on a variety of cells and tissues in addition to B cells. For instance, IL-6 induces hepatocytes to express various acute-phase proteins; activates osteoclasts to destroy bone tissue; functions as a growth factor for myeloma and plasmacytoma cells; increases platelet production; and precipitates fever and cachexia. IL-6 is therefore a multifunctional cytokine that plays roles in immune responses, inflammation, hematopoiesis, and the endocrine and nervous systems (Fig. 3).7,59–61)


Interleukin 6 in autoimmune and inflammatory diseases: a personal memoir.

Hirano T - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2010)

Multifunctional cytokine IL-6 is produced by a variety of cell types, including T cells, B cells, macrophages, astrocytes, stromal cells, vascular endothelial cells, smooth muscle cells, and fibroblasts. IL-6 induces antibody expression (B cell stimulatory factor 2) and cytotoxic T-lymphocyte activity (T cell activation factor). IL-6 was also referred to as a hybridoma/plasmacytoma growth factor and a hepatocyte stimulatory factor. IL-6 acts as a growth factor for AIDS-related Kaposi’s sarcoma, mesangial cells, and renal cell carcinomas, and as a thrombopoietin, a nerve growth factor, a hormone-inducing factor in the pituitary gland, an osteoclast-inducing factor, and a keratinocyte growth factor.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3066534&req=5

fig03: Multifunctional cytokine IL-6 is produced by a variety of cell types, including T cells, B cells, macrophages, astrocytes, stromal cells, vascular endothelial cells, smooth muscle cells, and fibroblasts. IL-6 induces antibody expression (B cell stimulatory factor 2) and cytotoxic T-lymphocyte activity (T cell activation factor). IL-6 was also referred to as a hybridoma/plasmacytoma growth factor and a hepatocyte stimulatory factor. IL-6 acts as a growth factor for AIDS-related Kaposi’s sarcoma, mesangial cells, and renal cell carcinomas, and as a thrombopoietin, a nerve growth factor, a hormone-inducing factor in the pituitary gland, an osteoclast-inducing factor, and a keratinocyte growth factor.
Mentions: I had wished to isolate the factor that stimulates B cells to produce immunoglobulin. Once we cloned the factor, however, it was clear that IL-6 acts on a variety of cells and tissues in addition to B cells. For instance, IL-6 induces hepatocytes to express various acute-phase proteins; activates osteoclasts to destroy bone tissue; functions as a growth factor for myeloma and plasmacytoma cells; increases platelet production; and precipitates fever and cachexia. IL-6 is therefore a multifunctional cytokine that plays roles in immune responses, inflammation, hematopoiesis, and the endocrine and nervous systems (Fig. 3).7,59–61)

Bottom Line: Characterization of IL-6 revealed a multifunctional cytokine that is involved in not only immune responses but also hematopoiesis, inflammation, and bone metabolism.F759 arthritis is dependent on CD4(+) T cells, IL-6, and IL-17A, and is enhanced by the pX gene product from human T cell leukemia virus 1 (HTLV-1).Furthermore, this interaction is mediated by the IL-6 amplifier through STAT3 and NF-kappaB.

View Article: PubMed Central - PubMed

Affiliation: JST-CREST, WPI Immunology Frontier Research Center, Osaka University, Japan. hirano@molonc.med.osaka-u.ac.jp

ABSTRACT
In this review, the author discusses the research that led to the identification and characterization of interleukin 6 (IL-6), including his own experience isolating IL-6, and the roles this cytokine has on autoimmune and inflammatory diseases. The cDNAs encoding B-cell stimulatory factor 2 (BSF-2), interferon (IFN)-beta2 and a 26-kDa protein were independently cloned in 1986, which in turn led to the identification of each. To resolve the confusing nomenclature, these identical molecules were named IL-6. Characterization of IL-6 revealed a multifunctional cytokine that is involved in not only immune responses but also hematopoiesis, inflammation, and bone metabolism. Moreover, IL-6 makes significant contributions to such autoimmune and inflammatory diseases as rheumatoid arthritis (RA).IL-6 activates both the STAT3 and SHP2/Gab/MAPK signaling pathways via the gp130 signal transducer. F759 mice, which contain a single amino-acid substitution in gp130 (Y759F) and show enhanced STAT3 activation, spontaneously develop a RA-like arthritis as they age. F759 arthritis is dependent on CD4(+) T cells, IL-6, and IL-17A, and is enhanced by the pX gene product from human T cell leukemia virus 1 (HTLV-1). Arthritis development in these mice requires that the F759 mutation is present in nonhematopoietic cells, but not in immune cells, highlighting the important role of the interaction between nonimmune tissues and the immune system in this disease. Furthermore, this interaction is mediated by the IL-6 amplifier through STAT3 and NF-kappaB. Ultimately, this model may represent a general etiologic process underlying other autoimmune and inflammatory diseases. More importantly, the understanding of IL-6 has paved the way for new therapeutic approaches for RA and other autoimmune and inflammatory diseases.

Show MeSH
Related in: MedlinePlus