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Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman’s disease
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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“Studies in the 1980s also showed that IL-6 is produced by cardiac myxoma cells (42) and Castleman’s germinal center cells (43)”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [43]
In the citing paper
“Generally, surgical removal of hyperplastic lymph nodes results in symptomatic improvement and reduced serum IL-6 concentrations (Yoshizaki et al., 1989”
From Targeting Interleukin-6 Signaling in Clinic (2019) · cites this paper as Yoshizaki et al., 1989
Citations
Cites
Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas
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“It was shown that the germinal centers of hyperplastic lymph nodes in patients with plasma cell CD produce large amounts of IL-6 [10].”
BackgroundAbsence of gallium uptake in unicentric and multicentric Castleman's disease.
Okamoto, I., Iyonaga, K., Fujii, K., Mori, T., Yoshioka, M., Kohrogi, H., Matsumoto, M., & Suga, M. (2003) · Internal medicine · doi:10.2169/internalmedicine.42.735 · Cited by 10
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“Together with these clinical data, MCD is known to result in a cachectic condition, with pyrexia, fatigue, and weight loss, due to IL6 overproduction by proliferative lymphoid tissues (25).”
BackgroundGu, Q.-H., Jia, X.-Y., Hu, S.-Y., Wang, S.-X., Zou, W., Cui, Z., & Zhao, M.-H. (2018) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2018.01.029 · Cited by 9
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“Pathogenesis‐ relevant activities, including the promotion of cell growth and induction of angiogenesis in support of B‐cell and endothelial neoplasia, par‐ allel the hypothesized role of hIL‐6 in MCD and KS [3,4,6,7].”
BackgroundFazakas, Á., Csire, M., Berencsi, G., Szepesi, Á., Matolcsy, A., Jakab, L., Karádi, I., & Várkonyi, J. (2009) · Leukemia and Lymphoma · doi:10.1080/10428190903162743 · Cited by 9
“Previous evidences may indicate that deregulated continous IL-6 production induces polyclonal plasmocytosis, leading to the generation of plasmocytoma/myeloma related monoclonality suspectedly with the additional expression of other oncogens eventually [8].”
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“The cytokine interleukin (IL)-6 plays an important role in the pathogenesis of CD; it regulates the immune response, hematopoiesis, and acute inflammatory phase (4, 5).”
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“The observed clinical symptoms of MCD are attributed to hypercytokinemia, including elevated levels of interleukin-6 (IL-6).([3]) MCD can be divided into the human herpesvirus 8 infection-related MCD and idiopathic MCD (iMCD).”
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“In TAFRO syndrome, there is an unfettered production of inflammatory cytokines such as IL-6 [11 ].”
BackgroundMacBeth, M., Joetham, A., Gelfand, E., & Schedel, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094582 · Cited by 7
“While IL-6 knockout mice have also been shown to present with heightened inflammatory responses with regional tissue damage [1,3], an excess of IL-6 is linked to Castleman’s disease [4], indicating the importance of the appropriate regulation of IL-6 levels.”
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“Interleukin 6 (IL-6) is a significant cytokine in the MCD pathogenesis,([6]) although the mechanisms underlying the IL-6 overproduction in MCD patients are not fully understood.”
BackgroundTargets of monoclonal antibodies for immunological diseases
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A case report of retroperitoneal pararenal Castleman’s disease associated with myasthenia gravis
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“In CD, the overproduction of IL-6, a product of activated T-lymphocytes, results in increased B-cell differentiation with the emergence of plasma cell clones and subsequent formation of autoantibodies that initiate immunopathological reactions [10,11].”
BackgroundCastleman Disease. A Report of Six Cases.
Fetica, B., Pop, B., Lisencu, C., Rancea, A., Coman, A., Cucuianu, A., & Petrov, L. (2014) · Clujul Medical · doi:10.15386/cjmed-302 · Cited by 7
“Interleukin-6 has been clearly linked to the pathogenesis, by acting as a promoter of the terminal B cell differentiation and by stimulation of plasma cell proliferation and production of immunglobulins [4,21].”
BackgroundInfluentialMucosal Hyperplasia in Infant With Jejunal Web
Rudolph, B., Ewart, M., Levin, T., Douglas, L. C., Borenstein, S., & Thompson, J. F. (2013) · Journal of Pediatric Gastroenterology and Nutrition - JPGN · doi:10.1097/mpg.0b013e3182638c1d · Cited by 7
Interleukin-6-producing undifferentiated thymic carcinoma with neuroendocrine features
Suzuki, M., Shinagawa, N., Oizumi, S., Fugo, K., & Nishimura, M. (2008) · Lung Cancer · doi:10.1016/j.lungcan.2008.07.018 · Cited by 8
Castleman's Disease: A Study of a Rare Lymphoproliferative Disorder in a University Hospital
Abdul-Rahman, I., Al-Amri, A., & Ghallab, K. (2009) · The Gulf journal of oncology · doi:10.4137/cmbd.s2161 · Cited by 7
Fragasso, A., Mannarella, C., Ciancio, A., Calvario, A., & Scarasciulli, M. (2008) · Leukemia and Lymphoma · doi:10.1080/10428190802389835 · Cited by 7
“The aetiology is poorly understood; the potential roles of HHV-8, also known as Kaposi sarcoma-associated herpes virus (KSHV), and Interleukin-6 (IL-6), responsible for the symptoms, are suggested in several studies [2,3].”
BackgroundKatsuki, K., Shinohara, K., Kameda, N., Yamada, T., Takeda, K., & Kamei, T. (1998) · Internal medicine · doi:10.2169/internalmedicine.37.973 · Cited by 7
Hyaline-vascular castleman disease: a rare cause of solitary subcutaneous soft tissue mass.
Naghashpour, M., Cualing, H., Szabunio, M., & Bui, M. (2010) · American journal of dermatopathology · doi:10.1097/dad.0b013e3181b7269a · Cited by 7
“In patients with PCCD, high levels of IL-6 have been demonstrated, which can also explain the systemic manifestations of the disease in these patients.(24) Furthermore, HHV-8 encodes a viral IL-6, which can induce endogenous human IL-6 secretion (therefore, contributes to plasmacytosis), vascular endothelial growth fa…”
BackgroundHigashikuni, Y., Mori, M., & Kino, H. (2007) · Internal medicine · doi:10.2169/internalmedicine.46.6003 · Cited by 7
“In fact, in cases of localized Castleman’s disease, clinical abnormalities may resolve after excision of the affected lymph nodes (11, 13, 17).”
BackgroundInfluentialStructure-Based Design of Small-Molecule Inhibitors of Human Interleukin-6
Joshi, A., Xiao, Z., Suman, S., Cooper, C. J., Ha, K., Agarwal, R., Carson, J. A., Quarles, L. D., Smith, J. C., & Gupta, M. (2025) · Molecules · doi:10.3390/molecules30142919 · Cited by 9
“It may be speculated that the role of hIL-6 in these two conditions is well-defined as increased concentration levels of hIL-6 are directly linked to the progression of the disease [15,36].”
Kakutani, T., Kamada, R., & Tamai, Y. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46100668 · Cited by 6
“Immunohistology in the lymph nodes of patients with iMCD and chemical analysis indicates that IL-6 is produced in the germinal centers of hyperplastic lymph nodes, and B cells and follicular dendritic cells in the germinal centers are the main sources of IL-6 [31].”
BackgroundAbe, N., Kono, M., Kono, M., Ohnishi, N., Sato, T., Tarumi, M., Yoshimura, M., Sato, T., Karino, K., Shimizu, Y., et al. (2021) · British Journal of Haematology · doi:10.1111/bjh.17993 · Cited by 6
Katsumata, Y., Ikari, J., Tanaka, N., Abe, M., Tsushima, K., Yonemori, Y., & Tatsumi, K. (2018) · Respiratory Medicine Case Reports · doi:10.1016/j.rmcr.2018.06.001 · Cited by 6
“In MCD, differentiation of B cells into plasma cells is promoted by IL-6 overproduction from the enlarged lymph node [1].”
BackgroundMinemura, H., Tanino, Y., & Ikeda, K. (2018) · BioResearch Open Access · doi:10.1089/biores.2017.0025 · Cited by 6
“47 uptake has been reported to be able to distinguish MCD from lymphoma.9 In MCD, replication and viraldependent hypercytokinemia are considered to be responsible for the clinicopathological findings of MCD, regardless of HIV infection.7,8,10,11 Interleukin (IL)-6 has been demonstrated to be expressed within the germi…”
BackgroundPerivesical unicentric Castleman disease initially suspected to be metastatic prostate cancer
Guthrie, P. J., Thomas, J. V., Peker, D., Turkbey, B., & Rais-Bahrami, S. (2016) · Urology Annals · doi:10.4103/0974-7796.177196 · Cited by 6
“[11] The symptomology of multicentric has been related to acute phase proteins, such as IL‑6 and C‑reactive protein, as well as an association between the human herpesvirus 8 and the hyperplastic lymphatic response of CD.[3] Though imaging modalities are commonly used to diagnosis pelvic masses, there are lacks radiol…”
BackgroundInfluentialSin, S.-H., Kang, S.-A., Kim, Y., Eason, A. B., Tan, K., An, H., & Dittmer, D. (2015) · Journal of Virology · doi:10.1128/jvi.02456-15 · Cited by 6
Anderson, S., Sasson, S., Lee, F., Cooper, W., Larsen, S., & Garsia, R. (2015) · BMC Infectious Diseases · doi:10.1186/s12879-016-1378-5 · Cited by 6
“Elevated circulating IL-6 derived from both host and HHV-8 is thought to contribute to the manifestations of a systemic inflammatory response [10, 11] and related laboratory findings [3].”
BackgroundKojima, M., Nakamura, N., Motoori, T., Shimizu, K., Haratake, J., & Nakamura, S. (2011) · International Journal of Surgical Pathology · doi:10.1177/1066896909331996 · Cited by 6
“Moreover, there were no clinical characteristics of PC type CD in either case.(2,3,18) Histopathological findings of idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia (IPL) showed similar to that of the present 2 cases.”
ResultKurosawa, S., Akiyama, N., Ohwada, A., Warabi, M., Suenaga, M., Kojima, M., & Tomiyama, J. (2009) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/hyp073 · Cited by 6
“In the present case, we chose corticosteroid treatment as the first-line therapy because various clinical manifestations of IPL are thought to be caused by overproduction of IL-6 (5,14,18).”
Loy, M., Perra, E., Siotto, P., Argiolas, A., Melis, A., Cianchetti, M. E., & Stefano, M. (2005) · Journal of Clinical Ultrasound · doi:10.1002/jcu.20139 · Cited by 6
“What relation could exist between the Castleman’s disease and Graves’ disease? It may be speculated that an exogenous antigen, viral or bacterial may simultaneously affect the thyroid gland and mesenteric node in genetically susceptible individuals, promoting an immune system dysregulation mediated by local production…”
BackgroundCastleman Disease: A Case with Atypical Presentation
Yarış, N., Çakır, M., Kalyoncu, M., Yıldız, K., & Okten, A. (2004) · Pediatric Hematology & Oncology · doi:10.1080/08880010490276908 · Cited by 6
“Systemic manifestations of the disease have been attributed to overproduction of interleukin-6 by the hyperplastic germinal centers of lymph nodes [4].”
BackgroundSystemic juvenile idiopathic arthritis mimics multicentric Castleman’s disease
Osone, S., Morimoto, A., Tsutsui, J., Kano, G., Todo, S., & Sugimoto, T. (2003) · Clinical Rheumatology · doi:10.1007/s10067-003-0797-z · Cited by 6
“Keywords Interleukin-6 Æ Lymphadenopathy Æ Multicentric Castleman s disease Æ Plasma cell Æ Systemic juvenile idiopathic arthritis Abbreviations CRP C-reactive protein Æ JIA Juvenile idiopathic arthritis Æ MCD Multicentric Castleman s disease”
BackgroundInfluentialB-CELL AND IMMUNOGLOBULIN IMMUNODEFICIENCY IN THE ELDERLY
Richmond, G., & Zeitz, H. (1993) · Immunology and allergy clinics of North America · doi:10.1016/s0889-8561(22)00413-1 · Cited by 6
Nakahama, H., Yokokawa, T., Okada, M., Miyazaki, M., Imai, N., Kubori, S., Nakanishi, T., Uyama, O., & Sugita, M. (1993) · Internal medicine · doi:10.2169/internalmedicine.32.189 · Cited by 6
Oksenhendler, É., Malphettes, M., Meignin, V., Boutboul, D., & Galicier, L. (2026) · British Journal of Haematology · doi:10.1111/bjh.70480 · Cited by 4
Barlingay, G., Findakly, D., Hartmann, C., & Amar, S. (2020) · Cureus · doi:10.7759/cureus.7589 · Cited by 5
Castleman disease of the neck: A case report.
Pasha, H., Siddiqui, M., & Wasif, M. (2020) · JPMA. The Journal of the Pakistan Medical Association · doi:10.5455/jpma.13110 · Cited by 5
Ekinci, R. M. K., Balcı, S., Ergin, M., Kupeli, S., Bayram, I., Yılmaz, M., & Kocabaş, E. (2019) · Journal of pediatric hematology/oncology · doi:10.1097/mph.0000000000001557 · Cited by 5
Vassos, N., Raptis, D., Lell, M., Klein, P., Perrakis, A., Köhler, J., Croner, R., Hohenberger, W., & Agaimy, A. (2016) · Archives of medical science : AMS · doi:10.5114/aoms.2016.57600 · Cited by 5
“Increased serum IL-6 level is positively correlated with active disease [19], and removal of the CD mass may result in an abrupt drop in IL-6 levels and resolution of symptoms [20].”
BackgroundMulticentric Castleman's Disease in a Child Revealed by Chronic Diarrhea
Benmiloud, S., Chaouki, S., Atmani, S., & Hida, M. (2015) · Case Reports in Pediatrics · doi:10.1155/2015/689206 · Cited by 5
“The opportunistic presence of HHV-8, favored by immune perturbations, and the direct pathogenic role of HHV-8, in association with dysregulation of cytokines, were suggested by demonstrating that HHV-8 is able to produce an IL-6 homologue, above all [10, 11].”
BackgroundPediatric Castleman disease of the parotid.
Varsak, Y. K., Gul, Z., Yucel, H., & Ozer, A. (2014) · The Journal of craniofacial surgery (Print) · doi:10.1097/scs.0000000000000951 · Cited by 5
“To our knowledge, there is only 1 patient in the English literature who had herpetic lesions on the nasal tip and oral mucosa after nasal surgery.(5) As a conclusion, with this report, we aimed to share our clinic experience about this rare condition.”
BackgroundHara, M., Mizote, I., Nakaoka, Y., Tanaka, H., Asano, Y., Sakata, Y., & Komuro, I. (2011) · Annals of Hematology · doi:10.1007/s00277-010-1051-9 · Cited by 5
“We also speculated that acute elevation of IL-6 provides essential stimulatory cues to acute VEGF elevation, which may imply the risk of complication of Castleman’s disease [8, 9].”
BackgroundMori, K., Yoshida, K., Mihara, M., Ohsugi, Y., Nakagawa, Y., Hoshikawa, S., Ozaki, H., & Ito, S. (2009) · Autoimmunity · doi:10.1080/08916930802709141 · Cited by 5
Increase in soluble CD138 in bronchoalveolar lavage fluid of multicentric Castleman’s disease
Hasegawa, M., Betsuyaku, T., Yoshida, N., Nasuhara, Y., Kinoshita, I., Ohta, S., Itoh, T., Park, P. W., & Nishimura, M. (2007) · Respirology (Carlton South. Print) · doi:10.1111/j.1440-1843.2006.00967.x · Cited by 5
Okada, H., Kano, R., & Watanabe, S. (1999) · British Journal of Dermatology · doi:10.1046/j.1365-2133.1999.03185.x · Cited by 5
[Retroperitoneal Castleman's disease occurred around the bilateral upper ureters. A case report].
Iwamoto, Y., Ueda, H., Yamamoto, K., Kiura, H., Itoh, S., Hirai, K., Takasaki, N., & Katsuoka, Y. (1998) · Nihon Hinyokika Gakkai zasshi. The japanese journal of urology · doi:10.5980/jpnjurol1989.89.618 · Cited by 5
Choi, Y., Cousins, E., & Nicholas, J. (2021) · Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer · doi:10.1007/978-3-030-57362-1_11 · Cited by 5
A case of resected plasma cell type castleman's disease with intramediastinal lymph nodes spread.
Aoki, M., Otsuka, T., Yanagi, M., Yokomakura, N., Nagata, T., Nakamura, Y., & Sato, M. (2014) · Annals of Thoracic and Cardiovascular Surgery · doi:10.5761/atcs.cr.13-00011 · Cited by 5
Membranous nephropathy and pulmonary alveolar proteinosis.
Yamada, H., Miura, N., Kitagawa, W., Kashima, Y., Matsui, S., Ozeki, N., Nishikawa, K., & Imai, H. (2007) · Internal medicine · doi:10.2169/internalmedicine.46.0129 · Cited by 5
“Secondary PAP, which is independent of anti-GM-CSF antibody, has been reported in patients with hematological malignancies (10), pneumocystis carini pneumonia (11), and the secondary macrophage dysfunction to inhalation of silica or titanium (12, 13).”
BackgroundEffect of anticancer drugs on the release of interleukin-6 in vitro
Hasan, S. I., Blaney, B., & Turk, J. L. (2005) · Cancer Immunology and Immunotherapy · doi:10.1007/bf01741790 · Cited by 5
“Abrlormal IL-6 activity is believed to be the cause of the systemic manifestations in patients with cardiac myxoma tumours [19] and in Castleman's disease [39].”
BackgroundA Case of Multicentric Castleman's Disease.
Hirano, T., Kurono, Y., Ichimiya, I., & Mogi, G. (1997) · doi:10.5631/jibirin.90.463 · Cited by 5
Giovannico, L., Santobuono, V., Fischetti, G., Mazzone, F., Parigino, D., Savino, L., Alfeo, M., Milano, A. D., Guaricci, A., Ciccone, M. M., et al. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14155369 · Cited by 4
Wang, S.-T., Wang, Q.-P., Li, J., Zhang, T.-H., Zhang, L., & Mao, Y.-Y. (2019) · Medicine · doi:10.1097/md.0000000000015039 · Cited by 4
“Secondary amyloidosis is believed to be caused mainly by chronic inflammation, and large amounts of IL-6 produced in the germinal center of CD may enhance the production of precursor of amyloid.([10,11]) Intrapulmonary CD is exceedingly rare,([12]) and differential diagnosis includes all types of tumors, like lung car…”
BackgroundMulticentric Plasma Cell Type of Castleman Disease in a Child: Difficulty in Diagnosis and Treatment
Karapınar, T., Tüfekçi, Ö., Gözmen, S., Yılmaz, Ş., Irken, G., & Ören, H. (2013) · Journal of pediatric hematology/oncology · doi:10.1097/mph.0b013e31829cdd2a · Cited by 4
Hyaline Vascular Castleman Disease Involving Renal Parenchyma and a Lymph Node: A Case Report
Kwon, J., Min, S., Shin, M., Lee, Y., Lee, Y.-G., & Ko, Y. (2012) · The Korean Journal of Pathology · doi:10.4132/koreanjpathol.2012.46.1.79 · Cited by 4
“Moreover, other exogenous or endogenous factors may induce IL-6 secretion from B lymphocytes in HHV-8 negative CD.(12) Nearly all HIV-positive patients and about half of HIVnegative patients with MCD have evidence of HHV-8 infection.”
BackgroundInfluentialCárdenas, V., Vitiello, M., Miteva, M., Amano, M., Romanelli, P., & Kerdel, F. (2011) · International Journal of Dermatology · doi:10.1111/j.1365-4632.2009.04442.x · Cited by 4
Multicentric Castleman's Disease in a Hepatitis C-Positive Intravenous Drug User: A Case Report
Talukder, D., & Delpachitra, S. (2011) · Case Reports in Medicine · doi:10.1155/2011/567840 · Cited by 4
“Thus, MCD may present with additional constitutional symptoms including fever, hepatomegaly, anaemia, weight loss, and loss of appetite, primarily through the action of IL-6 [2].”
InfluentialAMYLOID A AMYLOIDOSIS AND RENAL FAILURE IN A COURSE OF CASTLEMAN DISEASE
Sydor, A., Madura, M., Wagrowska-Danilewicz, M., Nowak, J., & Nowicki, M. (2007) · Nephrology · doi:10.1111/j.1440-1797.2007.00841.x · Cited by 4
“The geminal centres of hyperplastic lymph nodes in CD may produce Il-6 and their removal leads to a clinical improvement and decrease of Il-6.(8)”
BackgroundCD56‐Positive Cutaneous Lymphoma with Multicentric Castleman's Disease‐like Systemic Manifestations
Amo, Y., Ogata, F., Okabe, S., Yonemoto, K., & Katsuoka, K. (2001) · Journal of dermatology (Print) · doi:10.1111/j.1346-8138.2001.tb00071.x · Cited by 4
Elevated plasma fibrinogen in clinically asymptomatic unicentric Castleman's disease: a case report.
Bauters, A., Rogosnitzky, M., Hachulla, E., Copin, M., Saudemont, A., & Zerbib, P. (2014) · Journal of Clinical and Experimental Hematopathology · doi:10.3960/jslrt.54.85 · Cited by 4
Interleukin-6 in autoimmune diseases
Graeve, L., Baumann, M., & Heinrich, P. (2004) · Clinical Investigation · doi:10.1007/bf00184499 · Cited by 4
Molecular Aspects of Cancer and its Therapy
Mackiewicz, A., & Sehgal, P. (1998) · MCBU Molecular and Cell Biology Updates · doi:10.1007/978-3-0348-8946-9 · Cited by 4
“remodeling of the extracellular matrix [8], and the induction of the host's angiogenic response [9] take place in both primary tumors and metastatic lesions.”
BackgroundInfluentialInsights from Interleukin-6 trans-signaling and implications for the control of cytokine activity
Rose‐John, S. (2026) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2026.120109 · Cited by 3
Immunology and targeted therapy in Castleman disease
Tsunoda, S., Harada, T., Kikushige, Y., Kishimoto, T., & Yoshizaki, K. (2024) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2024.2357689 · Cited by 4
“Immunostaining of lymph nodes revealed that it is produced by B cells and follicular dendritic cells in the GC of hyperplastic lymph nodes [12].”
InfluentialSelf-citationTAFRO Syndrome: A Syndrome or a Subtype of Multicentric Castleman Disease?
Takai, K. (2024) · Biomedicines · doi:10.3390/biomedicines12030652 · Cited by 3
“Dysregulated overproduction of interleukin-6 (IL–6) is implicated in the pathogenesis of PC type MCD [29], and anti-IL-6 receptor antibody is highly effective for MCD in Japan [30].”
BackgroundSumiyoshi, R., Koga, T., Fukui, S., Furukawa, K., Momoki, M., Ichinose, K., Yano, S., & Kawakami, A. (2023) · Clinical Immunology · doi:10.1016/j.clim.2023.109798 · Cited by 5
Proteomic approaches to investigate gammaherpesvirus biology and associated tumorigenesis
Chappell, D. L., White, M. C., & Damania, B. (2020) · Advances in virus research · doi:10.1016/bs.aivir.2020.10.001 · Cited by 4
Synchronous retroperitoneal Castleman’s disease with clear cell renal cell carcinoma
Vishwajeet, V., Kakkar, N., Singhal, P., & Mandal, A. (2019) · BMJ Case Reports · doi:10.1136/bcr-2019-230919 · Cited by 3
Fujimoto, S., Sakai, T., Kawabata, H., Kurose, N., Yamada, S., Doai, M., Matoba, M., Iwao-Kawanami, H., Kawanami, T., Mizuta, S., et al. (2019) · Internal medicine · doi:10.2169/internalmedicine.2738-19 · Cited by 3
“and cause systemic inflammation and lymphadenopathy (2).”
BackgroundUnicentric Castleman disease in the mediastinum
Wala, S. J., Fallon, E. M., Forlenza, C., Shukla, N., & LaQuaglia, M. (2018) · Journal of Pediatric Surgery Case Reports · doi:10.1016/j.epsc.2018.05.005 · Cited by 3
Unicentric Castleman’s Disease: Case Report and Literature Review
Rivera, A. M. R. (2018) · doi:10.19080/ctoij.2018.09.555775 · Cited by 3
“Thus, another treatment modality that has been proposed is the blockage of the IL-6 dysregulated overproduction [7,11], especially in patients with plasma-cell variant [11] & Ren et al.”
BackgroundNon-cirrhotic portal hypertension associated with multicentric Castleman’s disease: a case report
Pinto, A. L., Gomes, M., Cipriano, M., & Ribeiro, M. (2017) · Acta oncologica · doi:10.1080/0284186x.2017.1404637 · Cited by 3
“Newer therapies, such as siltuximab, an anti-interleukin 6 (IL-6) monoclonal antibody are now recommended [9,10], in light of the known association between Castleman’s disease and IL-6 [11].”
BackgroundHyaline-Vascular Type Castleman’s Disease, Sarcoidosis, and Crohns Disease
Gupta, A., Ayyar, B., Zia, H. M., Chen, W.-N., Harris, S., & Naina, H. (2016) · Indian Journal of Hematology and Blood Transfusion · doi:10.1007/s12288-015-0580-8 · Cited by 3
Yang, M.-L., Wang, F.-D., Han, B., Wang, S.-J., Zhou, D.-B., Pan, H., Zhao, Y.-Q., Cui, Q.-C., Ma, L., Chng, W., et al. (2010) · Acta Haematologica · doi:10.1159/000322119 · Cited by 3
Cervical Castleman's disease associated with benign M-proteinemia: Report of a case
Komatsu, M., Ehara, T., & Kuroda, T. (1996) · Surgery today (Print) · doi:10.1007/bf00311511 · Cited by 3
Mito, M., Takahashi, M., Suda, T., Yagisawa, K., Shinada, S., Moriyama, Y., & Shibata, A. (1991) · doi:10.1002/ajh.2830360121 · Cited by 3
Song, N.-S. J., & Yoshizaki, K. (2012) · Inflammation and Regeneration · doi:10.2492/inflammregen.32.099 · Cited by 3
Self-citationUnicentric Castleman disease in the left adrenal region: a case report and literature review
Wang, Z., Shi, Y., Chen, Y., Xu, Z., Zheng, L., Zhang, Y.-B., & Xi, J. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1638855 · Cited by 2
Suzuki, K., Akiyama, M., Saito, K., Shimanuki, K., & Kaneko, Y. (2025) · Rheumatology International · doi:10.1007/s00296-025-05880-w · Cited by 4
“It has been reported that IL-6 is produced from B cells at the affected lymph nodes in iMCD [ 25, 26], consistent with our case.”
Hebisawa, Y., Ohta, A., Sekimoto, R., Sakurai, N., & Setoguchi, K. (2025) · Internal medicine · doi:10.2169/internalmedicine.4906-24 · Cited by 2
“The pathogenesis of iMCD remains unclear, but interleukin-6 is considered to play an important role (1).”
Naruse, S., Takashima, S., Fujita, Y., Kataoka, H., Kawamura, N., Natsuga, K., & Ujiie, H. (2024) · Journal of dermatology (Print) · doi:10.1111/1346-8138.17172 · Cited by 2
Idiopathic Multicentric Castleman Disease Presenting With Hypertensive Choroidopathy: A Case Report
Mimoto, T., Hashida, N., & Nishida, K. (2023) · Cureus · doi:10.7759/cureus.33368 · Cited by 2
“MCD is classified into a hyaline-vascular type, plasma cell type, and mixed type based on histopathology [2-4].”
BackgroundOveractive STAT3 drives accumulation of disease-associated CD21 low B cellsPreprint
Masle‐Farquhar, E., Peters, T. J., Jackson, K., Singh, M., Ma, C. S., Suan, D., Uzel, G., Chua, I. C., Leiding, J. W., Heiskanen, K., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.12.20.473595 · Cited by 3
“…autoimmune thyroid disease (AITD) (Lakatos et al., 1997, Figueroa-Vega et al., 2010), Behçet disease (Akman-Demir et al., 2008), Castleman’s disease (Yoshizaki et al., 1989), rheumatoid arthritis (RA) (Hirano et al., 1988), systemic lupus erythematosus (SLE) (Linker-Israeli et al., 1991) and…”
BackgroundTakata, S., Takeda, Y., Hirata, H., Shirai, Y., Morita, T., Futami, Y., Naito, Y., Masuhiro, K., Shiroyama, T., Miyake, K., et al. (2022) · Journal of Thoracic Disease · doi:10.21037/jtd-21-1973 · Cited by 2
“Although the etiology of iMCD remains unclear, interleukin-6 (IL-6) plays a key role in the pathogenesis and symptomatology of the disease (4).”
Coelho, V., Surendran, S., Roopavathana, B., & Chase, S. (2020) · BMJ Case Reports · doi:10.1136/bcr-2020-236056 · Cited by 2
A case of Castleman disease and literature review
Jiang, J., Hao, T.-F., Chen, J.-Y., Yang, S., Li, J., Huang, C.-M., Li, M., Wu, W., Zhang, C.-H., & He, Y.-L. (2020) · Digestive Medicine Research · doi:10.21037/dmr-20-49 · Cited by 2
“Yoshizaki (6) treated 7 patients with MCD with human recombinant Anti-IL-6 receptor antibody, the systemic symptoms were improved.”
BackgroundSrivastava, H., Reddy, D. S., Shah, S. N., & Shah, V. (2020) · Journal of Oral and Maxillofacial Pathology · doi:10.4103/jomfp.jomfp_283_20 · Cited by 2
“However, investigations have shown no evidence of any infectious disease.[10] The role of interleukin (IL-6) was suggested by the finding of increased IL-6 production by germinal centers in angio-follicular hyperplasia.”
BackgroundTAFRO syndrome complicated with occlusion of multiple cerebral arteries
Iwasaki, T., Nakamura, Y., Nakayama, S., Koita, N., Maki, T., Iemura, Y., Haga, H., Okada, T., Akizuki, S., Kuramoto, N., et al. (2018) · Modern Rheumatology Case Reports · doi:10.1080/24725625.2018.1469819 · Cited by 2
“Castleman’s disease is a benign lymphoproliferative disorder mediated by dysregulated cytokine production, particularly interleukin-6 (IL-6) [1].”
BackgroundInfluential
Metadata
- Authors
- Yoshizaki, K., Matsuda, T., Nishimoto, N., Kuritani, T., Taeho, L., Aozasa, K., Nakahata, T., Kawai, H., Tagoh, H., & Komori, T.
- Affiliations
- The University of Osaka (JP)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 1989-09-01
- Volume
- 74
- Issue
- 4
- Pages
- 1360-1367
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1632068222
- Cited by
- 928
- References
- 0
- Citations by year
- 2026: 11 · 2025: 27 · 2024: 23 · 2023: 15 · 2022: 29 · 2021: 20 · 2020: 32 · 2019: 18 · 2018: 33 · 2017: 37 · 2016: 21 · 2015: 38 · 2014: 35 · 2013: 34 · 2012: 25
- FWCI
- 14.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphadenopathy Diagnosis and Analysis
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Keywords
- Castleman disease, interleukin-6, germinal center, B cells, lymph node hyperplasia, hypergammaglobulinemia, acute phase proteins, plasma cell infiltration, surgical resection, cytokine production
- MeSH terms
- Adolescent, Female, Castleman Disease, Humans, Interleukins, Lymph Node Excision, Lymph Nodes, Lymphatic Diseases, Middle Aged, Interleukin-6
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