{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T06:11:54Z","timestamp":1784700714844,"version":"3.55.0"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T00:00:00Z","timestamp":1729641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["eJHaem"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Castleman disease (CD) represents a spectrum of heterogeneous lymphoproliferative disorders sharing peculiar histopathological features, clinically subdivided into unicentric CD (UCD) and multicentric CD (MCD) and presenting with variable inflammatory symptoms. Interleukin (IL)\u20106 and other cytokines play a major role in mediating CD inflammatory manifestations. Although the local microenvironment seems to be among the major sources of hypercytokinemia, the precise cellular origin of IL\u20106 production in CD is still debated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A series of five nodal CD of different subtypes (one UCD, two idiopathic MCDs [iMCDs], one HIV\u2010negative human herpesvirus 8 (HHV8)\u2010associated MCD, and one HIV\u2010positive HHV8\u2010associated MCD) and a non\u2010CD reactive control were tested using RNAscope analysis and a dual in situ hybridization (ISH)\/immunohistochemistry technique, in order to quantify IL\u20106 expression and its spatial distribution. Quantitative analyses of in situ mRNA were performed on digitalized slides using the HISTOQUANT software (3DHISTECH) and differences between cases were evaluated by the Kruskal\u2010Wallis test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>RNA\u2010ISH documented increased <jats:italic>IL\u20106<\/jats:italic> expression in all CD lymph nodes, independently from clinical and pathological subtypes, however, the highest levels were found in HHV8+ cases and statistically significant differences in IL\u20106 expression were found only between HHV8+ MCD and control case. Dual RNA\u2010ISH for <jats:italic>IL6<\/jats:italic> coupled with immunohistochemistry analysis showed that IL\u20106 was overexpressed in CD31\u2010positive endothelial cells in 5\/5 CD tested cases but not in the control case.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings suggest that nodal IL\u20106 expression seems to be significantly upregulated in HHV8+ MCD, but a trend toward increased nodal IL\u20106 expression was noticed also in UCD and iMCD\u2010not otherwise specified. CD31+ endothelial cells probably represent one of the major sources of IL\u20106 production in the nodal microenvironment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jha2.1034","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T13:40:59Z","timestamp":1729690859000},"page":"1182-1189","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Interleukin\u20106 transcripts up\u2010regulation in lymph nodes from unicentric and multicentric Castleman disease"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6244-3646","authenticated-orcid":false,"given":"Marco","family":"Lucioni","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"},{"name":"Pathology Unit, Fondazione IRCCS Policlinico \u201cSan Matteo\u201d  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3400-8732","authenticated-orcid":false,"given":"Gaia","family":"Morello","sequence":"additional","affiliation":[{"name":"Department of Sciences for Health Promotion and Mother\u2010Child Care \u201cG.D'Alessandro\u201d Tumor Immunology Unit University of Palermo  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5757-3569","authenticated-orcid":false,"given":"Caterina","family":"Cristinelli","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7932-8185","authenticated-orcid":false,"given":"Sara","family":"Fraticelli","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"},{"name":"Pathology Unit, Fondazione IRCCS Policlinico \u201cSan Matteo\u201d  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8675-1897","authenticated-orcid":false,"given":"Giuseppe","family":"Neri","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4985-339X","authenticated-orcid":false,"given":"Erica","family":"Travaglino","sequence":"additional","affiliation":[{"name":"Pathology Unit, Fondazione IRCCS Policlinico \u201cSan Matteo\u201d  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9468-9802","authenticated-orcid":false,"given":"Marco","family":"Minetto","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0930-4055","authenticated-orcid":false,"given":"Francesca","family":"Antoci","sequence":"additional","affiliation":[{"name":"Pathology Unit, Fondazione IRCCS Policlinico \u201cSan Matteo\u201d  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Libretti","sequence":"additional","affiliation":[{"name":"SynLab Italia Srl  Castenedolo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Gambacorta","sequence":"additional","affiliation":[{"name":"IRCCS SynLab SDN  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9504-991X","authenticated-orcid":false,"given":"Luca","family":"Arcaini","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"},{"name":"Division of Hematology Fondazione IRCCS Policlinico \u201cSan Matteo\u201d  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0821-6231","authenticated-orcid":false,"given":"Claudio","family":"Tripodo","sequence":"additional","affiliation":[{"name":"Department of Sciences for Health Promotion and Mother\u2010Child Care \u201cG.D'Alessandro\u201d Tumor Immunology Unit University of Palermo  Palermo Italy"},{"name":"Tumor and Microenvironment Histopathology Unit The FIRC Institute of Molecular Oncology IFOM  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2454-5980","authenticated-orcid":false,"given":"Marco","family":"Paulli","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"},{"name":"Pathology Unit, Fondazione IRCCS Policlinico \u201cSan Matteo\u201d  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,23]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375\u2010022\u201001620\u20102"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000931"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003334"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15019"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-10-746933"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2017.09.009"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00317-7"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2017.09.004"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics11112008"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(16)00006-5"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000526640"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2017.09.002"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-12-545087"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2010-0212"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2014.11.003"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V78.11.2923.2923"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428190009087030"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.12.4034.412k38_4034_4043"},{"issue":"6","key":"e_1_2_13_20_1","first-page":"1517","article-title":"Expression of a virus\u2010derived cytokine, KSHV vIL\u20106, in HIV\u2010seronegative Castleman's disease","volume":"151","author":"Parravicini C","year":"1997","journal-title":"Am J Pathol"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-19-0521"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1159\/000505099"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.46.6262"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(14)70319\u20105"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-021-00950-3"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2021.280370"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2011.08.002"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2017.09.003"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25123"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-07-862334"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.2002.2012"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.24068"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-021-01603-6"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.101562"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24097813"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2021.155654"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2014.01.008"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.943354"},{"issue":"7","key":"e_1_2_13_39_1","first-page":"626","article-title":"Synergy between IL\u20106 and TGF\u2010\u03b2 signaling promotes FOXP3 degradation","volume":"5","author":"Gao Z","year":"2012","journal-title":"Int J Clin Exp Pathol"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12061328"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231810301"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.19334"}],"container-title":["eJHaem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jha2.1034","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T12:50:00Z","timestamp":1734353400000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jha2.1034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,23]]},"references-count":41,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/jha2.1034"],"URL":"https:\/\/doi.org\/10.1002\/jha2.1034","archive":["Portico"],"relation":{},"ISSN":["2688-6146","2688-6146"],"issn-type":[{"value":"2688-6146","type":"print"},{"value":"2688-6146","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,23]]},"assertion":[{"value":"2024-07-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}