Increased Expression of Vascular Endothelial Growth Factor (VEGF) in Castleman's Disease: Proposed Pathomechanism of Vascular Proliferation in the Affected Lymph Node

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Abstract
Castleman's disease is a lymphoproliferative disorder of unknown etiology characterized by enlarged hyperplastic lymph nodes with marked vascular proliferation. To evaluate the possible involvement of vascular endothelial growth factor (VEGF) in the pathogenesis of Castleman's disease, we studied VEGF expression in sera and lymph nodes from four patients with either the plasma-cell type or mixed type of Castleman's disease. Clinically, one patient had the multicentric type and the others the localized type. The VEGF levels of the sera and the supernatants of the cultured lymph nodes were higher than those of normal controls. VEGF was strongly expressed in plasma cells in the interfollicular region of the lymph nodes, but rarely in normal lymph nodes. The disregulated IL-6 gene expression is considered to be a primary event that could be related to the etiology of this disease. Recently, Kaposi's sarcoma virus / human herpes virus 8 (KSHV/HHV-8) has been reported to be associated with a subset of the multicentric type of Castleman's disease, and a viral homologue of IL-6 (vIL-6) encoded by KSHV/HHV-8 has been shown to induce VEGF expression. Human IL-6 produced in the affected lymph nodes of Castleman's disease may induce paracrine VEGF-production by plasma cells and vascular proliferation in the lymph node. The confirmation of the role of VEGF in the pathogenesis of Castleman's disease may provide a therapeutic strategy.