IL-6 in autoimmune disease and chronic inflammatory proliferative disease

Ishihara, Katsuhiko; Hirano, Toshio

doi:10.1016/s1359-6101(02)00027-8

Cited by 721 publications

(528 citation statements)

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“…16.2 ± 6.7 296.6 ± 83.4*** 25.1 ± 2.1 376.0 ± 135.0**** Cytokine IL-17 (pg/mL) 0.42 ± 0.26 13.94 ± 3.60*** 0.25 ± 0.25 7.86 ± 1.70** IL-6 (pg/mL) 3.22 ± 0.67 4.92 ± 0.69 3.74 ± 1.14 14.7 ± 5.34**** other than BALB/c are resistant [26,27]. B6 IL-6 Tg mouse was reported to show a progression from polyclonal plasmacytosis to fully transformed monoclonal plasmacytoma when backcrossed to BALB/c mice [13,23].…”

Section: Discussionmentioning

confidence: 99%

“…Genetic background is an important factor for plasmacytomagenesis [25,26]. Mouse plasmacytoma induced by pristane oil (2,6,10,12-tetramethylpentadecane) is the most widely used and accepted model and has provided the most data on plasmacytomagenesis so far [25].…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…IL-6 Tg mice develop a massive polyclonal plasmacytosis [23] and plasmacytoma [13]. In contrast, IL-6-deficient mice do not develop plasmacytoma [24], which indicates the critical role played by IL-6 in murine plasmacytomagenesis.Genetic background is an important factor for plasmacytomagenesis [25,26]. Mouse plasmacytoma induced by pristane oil (2,6,10,12-tetramethylpentadecane) is the most widely used and accepted model and has provided the most data on plasmacytomagenesis so far [25].…”

mentioning

confidence: 99%

“…Mouse plasmacytoma induced by pristane oil (2,6,10,12-tetramethylpentadecane) is the most widely used and accepted model and has provided the most data on plasmacytomagenesis so far [25]. Furthermore, susceptibility to pristane-induced plasmacytomagenesis is genetically determined and mouse strains 91.9 ± 15.8 274.4 ± 51.4* 96.8 ± 32.5 1680.6 ± 318.9** IgG1 (mg/dL) 31.8 ± 6.9 71.6 ± 11.3*** 41.8 ± 10.5 587.6 ± 97.2** IgG2a (mg/dL) 1.0 ± 0.1 1.0 ± 0.1 3.7 ± 1.5 189.2 ± 89.1**** IgG2b (mg/dL) 15.5 ± 4.5 67.1 ± 10.4* 13.4 ± 1.5 161.8 ± 9.5** IgG3 (mg/dL) 24.1 ± 3.8 50.6 ± 19.3 17.1 ± 3.4 139.0 ± 35.4**** IgA (mg/dL)16.2 ± 6.7 296.6 ± 83.4*** 25.1 ± 2.1 376.0 ± 135.0**** Cytokine IL-17 (pg/mL) 0.42 ± 0.26 13.94 ± 3.60*** 0.25 ± 0.25 7.86 ± 1.70** IL-6 (pg/mL) 3.22 ± 0.67 4.92 ± 0.69 3.74 ± 1.14 14.7 ± 5.34**** other than BALB/c are resistant [26,27]. B6 IL-6 Tg mouse was reported to show a progression from polyclonal plasmacytosis to fully transformed monoclonal plasmacytoma when backcrossed to BALB/c mice [13,23].…”

mentioning

confidence: 99%

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Overexpression of RORγt under control of the CD2 promoter induces polyclonal plasmacytosis and autoantibody production in transgenic mice

et al. 2012

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Retinoic acid related orphan receptor gamma-t (RORγt) is known to be a master regulator of Th17-cell development. In this study, we generated RORγt-overexpressing transgenic (RORγt Tg) mice in which transgene expression was driven by the CD2 promoter, and found that these mice developed polyclonal plasmacytosis and autoantibody production. RORγt Tg mice were generated on a C57BL/6 background, and also were intercrossed with BALB/c mice. BALB/c F1 (BALB/F1) RORγt Tg mice developed massive polyclonal plasmacytosis, and had shorter life spans. Splenomegaly and infiltration of plasma cells into the lung were observed. Hyperglobulinemia, anti-double-stranded DNA antibodies, antierythrocyte antibodies, and anti-platelet antibodies were detected in BALB/F1 RORγt Tg mice. In the present study, polyclonal plasmacytosis in BALB/F1 RORγt Tg mice appeared to be due to the induction of excessive IL-6 production by IL-17. We detected increased numbers of CD11b + cells that produced IL-6. We also generated IL-6-deficient RORγt Tg BALB/F1 background mice, which displayed high levels of serum IL-17, but did not develop severe hyperglobulinemia. Excessive IL-6 production by several cell types, including macrophages, in BALB/F1 RORγt Tg mice, might effect the development of plasmacytosis. These results suggest that RORγt plays important roles in the development of plasmacytosis and autoantibody production. Eur. J. Immunol. 2012Immunol. . 42: 1999Immunol. -2009 Introduction CD4 + T helper (Th) cells are a subcategory of T lymphocytes that play a central role in modulating immune responses. Classically, naïve CD4 + T cells have been thought to differentiate into two cell types, Th1 and Th2 cells. This corresponds to the Th1/Th2 paradigm proposed by Mosmann et al. [1]. More recently, a third subset of Th cells, Th17 cells, has been described; this is a distinct lineage that does not share developmental pathways with either Th1 or Th2 cells [2,3]. Th17 cells are generally thought to be proinflammatory, especially through the production of 3]. Th17 cells have been shown to participate in the development of autoimmunity, and also to play an important role in host defense against infection [4]. Expression of the transcription factor retinoic acid related orphan receptor gamma-t (RORγt) is required for the differentiation of Th17 cells [5,6]. The orphan receptor RORγt is a thymusspecific isoform of RORγ [7]. A related nuclear receptor, RORα, was shown to act in synergy with RORγt to promote the differentiation of Th17 cells [8]. STAT3 is also required for full generation of the Th17 lineage [9]. The upregulation of RORγt depends on STAT3 [9], and the selective deletion of STAT3 in T cells partially abrogates the development of Th17 cells because it also abrogates the expression of RORα and RORγt [8].IL-6 is an important cytokine in the differentiation of Th17 cells. IL-6, together with TGF-β, is required to induce IL-17 expression in naïve CD4 + T cells, which are characterized by the expression of RORγt [5,10,11]. Since its discovery i...

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