HUMAN-HERPESVIRUS TYPE-8 INTERLEUKIN-6 HOMOLOG IS FUNCTIONALLY ACTIVEON HUMAN MYELOMA CELLS

Seroepidemiology and polymerase chain reaction studies have strongly s uggested that human herpesvirus type 8 (HHV-8) is associated with Kapo si'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 differ entiation factor is known to play an essential role in the pathophysio logy of B-cell tumors. Thus, it seems possible that virus-encoded IL-6 contributes to malignant growth of HHV-8-positive B-cell lymphatic tu mors. We have tested a preparation of HHV-8-derived IL-6 for the abili ty 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 re quired much more protein on a weight basis when compared with hIL-6 fo r maximal proliferation. The proliferative effect of vIL-6 was almost completely inhibited by a combination of anti-IL-6 receptor (IL-6R) an d anti-gp130 antibodies or IL-6R superantagonist Sant7 and anti-gp130 antibodies, This report demonstrates that vIL-6 has proliferative acti vity on human cells and that the IL-6R and gp130 are involved in vIL-6 signaling in the myeloma cell line INA-6. (C) 1998 by The American So ciety of Hematology.