Interleukin-6 Transcripts Up-regulation in Lymph Nodes from Unicentric and Multicentric Castleman Disease

Overview

Journal EJHaem

Specialty Hematology

Date 2024 Dec 18

PMID 39691263

Authors

Marco Lucioni

Gaia Morello

Caterina Cristinelli

Sara Fraticelli

Giuseppe Neri

Erica Travaglino

Marco Minetto

Francesca Antoci

Paolo Libretti

Marcello Gambacorta

Luca Arcaini

Claudio Tripodo

Marco Paulli

Affiliations

Soon will be listed here.

Abstract

Introduction: 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)-6 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-6 production in CD is still debated.

Methods: A series of five nodal CD of different subtypes (one UCD, two idiopathic MCDs [iMCDs], one HIV-negative human herpesvirus 8 (HHV8)-associated MCD, and one HIV-positive HHV8-associated MCD) and a non-CD reactive control were tested using RNAscope analysis and a dual in situ hybridization (ISH)/immunohistochemistry technique, in order to quantify IL-6 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-Wallis test.

Results: RNA-ISH documented increased 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-6 expression were found only between HHV8+ MCD and control case. Dual RNA-ISH for coupled with immunohistochemistry analysis showed that IL-6 was overexpressed in CD31-positive endothelial cells in 5/5 CD tested cases but not in the control case.

Conclusion: Our findings suggest that nodal IL-6 expression seems to be significantly upregulated in HHV8+ MCD, but a trend toward increased nodal IL-6 expression was noticed also in UCD and iMCD-not otherwise specified. CD31+ endothelial cells probably represent one of the major sources of IL-6 production in the nodal microenvironment.

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