Human herpesvirus type 8 interleukin-6 homologue is functionally active on human myeloma cells

R. Burger, F. Neipel, B. Fleckenstein, R. Savino, G. Ciliberto, J. R. Kalden, M. Gramatzki

Research output: Contribution to journalArticle

Abstract

Seroepidemiology and polymerase chain reaction studies have strongly suggested that human herpesvirus type 8 (HHV-8) is associated with Kaposi's sarcoma, Castleman's disease, and body cavity-based lymphoma. The genome of HHV-8 harbors a viral analogue of the interleukin-6 (IL-6) gene. The amino acid sequence of the viral IL-6 (vIL-6) protein is 24.7% identical to human IL-6 (hIL-6). IL-6 as a B-cell growth and differentiation factor is known to play an essential role in the pathophysiology of B-cell tumors. Thus, it seems possible that virus-encoded IL-6 contributes to malignant growth of HHV-8-positive B-cell lymphatic tumors. We have tested preparation of HHV-8- derived IL-6 for the ability to promote the proliferation of the human myeloma cell line INA-6, which is strictly dependent on exogenous IL-6 for growth and survival. Viral IL-6 significantly induced DNA synthesis of INA-6 cells, but required much more protein on a weight basis when compared with hIL-6 for maximal proliferation. The proliferative effect of vIL-6 was almost completely inhibited by a combination of anti-IL-6 receptor (IL-6R) and anti- gp130 antibodies or IL-6R superantagonist Sent7 and anti-gp130 antibodies. This report demonstrates that vIL-6 has proliferative activity on human cells and that the IL-6R and gp130 are involved in vIL-6 signaling in the myeloma cell line INA-6.

Original languageEnglish
Pages (from-to)1858-1863
Number of pages6
JournalBlood
Volume91
Issue number6
Publication statusPublished - Mar 15 1998

ASJC Scopus subject areas

  • Hematology

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    Burger, R., Neipel, F., Fleckenstein, B., Savino, R., Ciliberto, G., Kalden, J. R., & Gramatzki, M. (1998). Human herpesvirus type 8 interleukin-6 homologue is functionally active on human myeloma cells. Blood, 91(6), 1858-1863.