Angiogenesis and hematopoiesis induced by Kaposi's sarcoma-associated herpesvirus-encoded interleukin-6 [see comments]

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Angiogenesis and hematopoiesis induced by Kaposi's sarcoma-associated herpesvirus-encoded interleukin-6 [see comments]

Blood. 1999 Jun 15;93(12):4034-43. Unique Identifier : AIDSLINE MED/99290757
Aoki Y; Jaffe ES; Chang Y; Jones K; Teruya-Feldstein J; Moore PS; Tosato G; Division of Hematologic Products, Center for Biologics Evaluation; and Research, Food and Drug Administration, Bethesda, MD, USA.; AOKI@CBER.FDA.GOV

Abstract: Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8 [HHV-8]) is a herpesvirus linked to the development of Kaposi's sarcoma (KS), primary effusion lymphoma, and a proportion of Castleman's disease. KSHV encodes viral interleukin-6 (vIL-6), which is structurally homologous to human and murine IL-6. The biological activities of vIL-6 are largely unknown. To gain insight into the biology of vIL-6, we expressed vIL-6 in murine fibroblasts NIH3T3 cells and inoculated stable vIL-6-producing clones into athymic mice. vIL-6 was detected selectively in the blood of mice injected with vIL-6-expressing clones. Compared with controls, vIL-6-positive mice displayed increased hematopoiesis in the myeloid, erythroid, and megakaryocytic lineages; plasmacytosis in spleen and lymph nodes; hepatosplenomegaly; and polyclonal hypergammaglobulinemia. vIL-6-expressing NIH3T3 cells gave rise to tumors more rapidly than did control cells, and vIL-6-positive tumors were more vascularized than controls. Vascular endothelial growth factor (VEGF) was detected at higher levels in the culture supernatant of vIL-6-expressing cells compared with controls, and immunohistochemical staining detected VEGF in spleen, lymph nodes, and tumor tissues from mice bearing vIL-6-producing tumors but not control tumors. Thus, vIL-6 is a multifunctional cytokine that promotes hematopoiesis, plasmacytosis, and angiogenesis. Through these functions, vIL-6 may play an important role in the pathogenesis of certain KSHV-associated disorders.

Keywords: JOURNAL ARTICLE Animal Endothelial Growth Factors/ANALYSIS Erythropoiesis Granulocytes *Hematopoiesis Hepatomegaly Herpesvirus, Kaposi Sarcoma-Associated/*GENETICS Human Interleukin-6/GENETICS/*PHARMACOLOGY Lymph Nodes/PATHOLOGY Lymphokines/ANALYSIS Megakaryocytes Mice Mice, Nude Neovascularization, Pathologic/*VIROLOGY Plasma Cells/PATHOLOGY Recombinant Proteins/PHARMACOLOGY Spleen/PATHOLOGY Splenomegaly Transfection 3T3 Cells
Comment in: Blood 1999 Jun 15;93(12):4031-3
990930
A9991280

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