Interleukin-6 transcripts up-regulation in lymph nodes from unicentric and multicentric Castleman disease

Area of Science:

• Hematology
• Immunology
• Pathology

Background:

• Castleman disease (CD) is a group of lymphoproliferative disorders with varied symptoms.
• Interleukin-6 (IL-6) is a key cytokine implicated in CD's inflammatory processes.
• The cellular origin of IL-6 in CD's microenvironment remains unclear.

Purpose of the Study:

• To investigate the cellular source of IL-6 in Castleman disease lymph nodes.
• To quantify IL-6 expression across different CD subtypes and controls.

Main Methods:

• RNAscope analysis and dual in situ hybridization/immunohistochemistry were used.
• Five nodal CD cases (UCD, iMCD, HHV8+ MCD, HIV+ HHV8+ MCD) and a control were analyzed.
• Quantitative mRNA analysis was performed using HISTOQUANT software.

Main Results:

• Increased IL-6 expression was observed in all CD lymph nodes.
• HHV8+ cases showed the highest IL-6 levels, with significant differences compared to controls.
• IL-6 was consistently overexpressed in CD31-positive endothelial cells in all tested CD cases.

Conclusions:

• Endothelial cells are likely a major source of IL-6 in the nodal microenvironment of CD.
• A trend of increased IL-6 was noted in UCD and iMCD, while HHV8+ MCD showed significant upregulation.
• Findings highlight the role of endothelial IL-6 in CD pathogenesis.