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Human Herpesvirus Type 8 Interleukin-6 Homologue Is Functionally
Active on Human Myeloma Cells
Renate Burger,
Frank Neipel,
Bernhard Fleckenstein,
Rocco Savino,
Gennaro Ciliberto,
Joachim R. Kalden, and
Martin Gramatzki
From the Division of Hematology/Oncology, Department of Medicine III,
the Institute for Clinical and Molecular Virology, University of
Erlangen-Nuernberg, Erlangen, Germany; and Istituto di Ricerche di
Biologia Molecolare P. Angeletti, Rome, Italy.
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 a 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 Sant7 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.
Blood, Vol. 91 No. 6 (March 15), 1998:
pp. 1858-1863
© 1998 by The American Society of Hematology.
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