PMID- 9490667 OWN - NLM STAT- MEDLINE DCOM- 19980409 LR - 20210216 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 91 IP - 6 DP - 1998 Mar 15 TI - Human herpesvirus type 8 interleukin-6 homologue is functionally active on human myeloma cells. PG - 1858-63 AB - 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. FAU - Burger, R AU - Burger R AD - Division of Hematology/Oncology, Department of Medicine III, the Institute for Clinical and Molecular Virology, University of Erlangen-Nuernberg, Erlangen, Germany. FAU - Neipel, F AU - Neipel F FAU - Fleckenstein, B AU - Fleckenstein B FAU - Savino, R AU - Savino R FAU - Ciliberto, G AU - Ciliberto G FAU - Kalden, J R AU - Kalden JR FAU - Gramatzki, M AU - Gramatzki M LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antigens, CD) RN - 0 (DNA, Neoplasm) RN - 0 (IL6ST protein, human) RN - 0 (Interleukin-6) RN - 0 (Membrane Glycoproteins) RN - 0 (Receptors, Interleukin-6) RN - 0 (Recombinant Proteins) RN - 0 (Viral Proteins) RN - 133483-10-0 (Cytokine Receptor gp130) SB - IM CIN - Blood. 1998 Sep 15;92(6):2186-8. PMID: 9731082 MH - Antibodies, Monoclonal/pharmacology MH - Antigens, CD/immunology/pharmacology MH - Cell Division/drug effects MH - Cytokine Receptor gp130 MH - DNA Replication/drug effects MH - DNA, Neoplasm/biosynthesis MH - Herpesvirus 8, Human/*physiology MH - Humans MH - Interleukin-6/*pharmacology MH - Membrane Glycoproteins/immunology/pharmacology MH - Multiple Myeloma/*pathology MH - Neoplastic Stem Cells/*drug effects MH - Polymerase Chain Reaction MH - Receptors, Interleukin-6/antagonists & inhibitors/drug effects/immunology MH - Recombinant Proteins/pharmacology MH - Tumor Cells, Cultured MH - Viral Proteins/*pharmacology EDAT- 1998/04/16 00:00 MHDA- 1998/04/16 00:01 CRDT- 1998/04/16 00:00 PHST- 1998/04/16 00:00 [pubmed] PHST- 1998/04/16 00:01 [medline] PHST- 1998/04/16 00:00 [entrez] AID - S0006-4971(20)54782-4 [pii] PST - ppublish SO - Blood. 1998 Mar 15;91(6):1858-63.