Pathogenic significance of Interleukin-6 (IL-6/BSF-2) in Castleman's Disease

Department of Medicine, Osaka University Medical School, Japan.
Blood (Impact Factor: 10.45). 10/1989; 74(4):1360-7.
Source: PubMed

ABSTRACT Castleman's disease is a syndrome consisting of giant lymph node hyperplasia with plasma cell infiltration, fever, anemia, hypergammaglobulinemia, and an increase in the plasma level of acute phase proteins. It has been reported that clinical abnormalities disappear after the resection of the affected lymph nodes, suggesting that products of lymph nodes may cause such clinical abnormalities. Interleukin-6 (IL-6) is a cytokine inducing B-cell differentiation to immunoglobulin-producing cells and regulating biosynthesis of acute phase proteins. This report demonstrates that the germinal centers of hyperplastic lymph nodes of patients with Castleman's disease produce large quantities of IL-6 without any significant production of other cytokines. In a patient with a solitary hyperplastic lymph node, clinical improvement and decrease in serum IL-6 were observed following surgical removal of the involved lymph node. There was a correlation between serum IL-6 level, lymph node hyperplasia, hypergammaglobulinemia, increased level of acute phase proteins, and clinical abnormalities. The findings in this report indicate that the generation of IL-6 by B cells in germinal centers of hyperplastic lymph nodes of Castleman's disease may be the key element responsible for the variety of clinical symptoms in this disease.

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Available from: Kazuyuki Yoshizaki, Feb 07, 2014
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    • "The etiology of CD is not fully elucidated. The role of IL-6 cytokine may be one of the key components in the pathophysiology of the disease, its overexpression in germinal center cells of the lymph nodes was shown in the plasma cell type of CD [24]. In mice IL-6 induced histological and clinical changes were specific to CD [25]. "
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    ABSTRACT: Virtual slides The virtual slide(s) for this article can be found here: Castleman disease (CD), described as a heterogeneous lymphoproliferative disorder, can be divided into different subtypes according to clinical appearance (unicentric and multicentric form) and histopathological features (hyaline vascular, plasma cell, mixed type, human herpesvirus 8–associated and multicentric not otherwise specified). Unicentric CD is known to be usually of the hyaline vascular variant, plasma cell and mixed type of this form are quite uncommon. Malignancies are mainly associated with the multicentric form. We report a rare case of unicentric mixed variant CD evolving into intrabronchial, extramedullary plasmacytoma. Intrabronchial mass with consequential obstruction of the left main bronchus, left lung atelectasis and mediastinal lymphadenomegaly was detected by chest CT in our patient suffering from cough and hemoptysis. Pulmonectomy was performed, histopathological and immunhistochemical analysis of lymph nodes revealed mixed type of CD with interfollicular monotypic plasma cell proliferation. The intrabronchial mass consisted of monotypic plasma cells confirming plasmacytoma. Systemic involvement was not confirmed by further tests. Although malignancies more often present in multicentric CD that usually belongs to the plasma cell subtype, this case confirms the neoplastic potential of the rarest, unicentric mixed variant of CD.
    Diagnostic Pathology 03/2014; 9(1):64. DOI:10.1186/1746-1596-9-64 · 2.60 Impact Factor
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    • "The pathogenesis of the hyaline-vascular type has yet to be elucidated, although alterations of the follicular dendritic cell networks have been reported [5]. On the other hand, elevated expression of interleukin-6 (IL-6) is considered to be related to the pathogenesis of the plasma cell type, explaining above-mentioned symptoms [6]. "
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    ABSTRACT: Unicentric Castleman's disease is a rare, benign lymphoproliferative disorder that is curable with surgical resection. However, significant bleeding often occurs during surgery because of tumor hypervascularity. We herein present a case of hyaline-vascular-type mediastinal unicentric Castleman's disease, successfully resected using video-assisted thoracoscopic surgery with preoperative embolization. In the present case, tumor hypervascularity and feeding vessels were revealed by computed tomography (CT), which led us to perform preoperative angiography and embolization to the tumor feeding arteries to reduce intraoperative bleeding. Castleman's disease should be considered in the differential diagnosis of hypervascular mediastinal tumors. Tumor vascularity should be assessed prior to surgery, and preoperative embolization should be considered.
    Case Reports in Medicine 09/2013; 2013(4):354507. DOI:10.1155/2013/354507
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    • "We have previously reported that transgenic mice with human interleukin-6 (hIL6) driven by the major histocompatibility complex class I H-2Ld gene promoter develop symptoms similar to Castleman's disease in human456 such as lymphadenopathy, massive immunoglobulin G1 plasmacytosis, splenomegaly, mesangial proliferative glomerulonephritis, thrombocytopenia, leukocytosis, anemia and muscle atrophy78. We also demonstrated that a mAb to mouse IL-6 receptor, the surrogate antibody MR16-1, completely blocked their symptoms8. "
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    ABSTRACT: For clinical trials of therapeutic monoclonal antibodies (mAbs) to be successful, their efficacy needs to be adequately evaluated in preclinical experiments. However, in many cases it is difficult to evaluate the candidate mAbs using animal disease models because of lower cross-reactivity to the orthologous target molecules. In this study we have established a novel humanized Castleman's disease mouse model, in which the endogenous interleukin-6 receptor gene is successfully replaced by human IL6R, and human IL6 is overexpressed. We have also demonstrated the therapeutic effects of an antibody that neutralizes human IL6R, tocilizumab, on the symptoms in this mouse model. Plasma levels of human soluble IL6R and human IL6 were elevated after 4-week treatment of tocilizumab in this mouse model similarly to the result previously reported in patients treated with tocilizumab. Our mouse model provides us with a novel means of evaluating the in vivo efficacy of human IL6R-specific therapeutic agents.
    Scientific Reports 02/2013; 3:1196. DOI:10.1038/srep01196 · 5.58 Impact Factor
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