Human interleukin-6 is in vivo an autocrine growth factor for human herpesvirus-8-infected malignant B lymphocytes.
Human interleukin-6 (hIL-6) acts as a growth factor in several human B lymphoid cancers. As human herpesvirus-8 (HHV-8) encodes for a viral IL-6 (vIL-6), the viral cytokine may be responsible for several manifestations of HHV-8-related disorders. Using an anti-hIL-6 mAb (B-E8) which does not recognize vIL-6, we investigated the involvement of the human cytokine in the proliferation of HHV-8-positive primary effusion lymphoma (PEL) cells. In vitro, 5/5 PEL cell lines produced hIL-6 (4 to 1,200 pg/ml). The EBV- HHV-8+ cell line (BCBL-1) was adapted to grow in SCID mice. hIL-6 was detected in the serum of mice with grafts, as well as human soluble CD138 (sCD138) and human IL-10 (hIL-10). The serum level of these mediators increased with tumor progression. The effect of treatment with the B-E8 mAb on the tumor progression and survival was evaluated. This treatment significantly slowed down the tumor development: on day 54, there were more mice with low levels of sCD138 and hIL-10 in the treated group than in controls (p = 0.03 and 0.02, respectively); treatment also delayed death (median date of death was day 65 for control mice and day 84 for anti-hIL-6 mAb-treated mice; p < 0.02). Thus, hIL-6 is expressed in addition to vIL-6 in HHV-8-positive malignant B lymphocytes, and the viral cytokine does not totally substitute for human IL-6 in promoting tumor progression.
Foussat
A
A
INSERM U. 131, Institut Paris-Sud sur les Cytokines, 32, rue des Carnets, 92140 Clamart, France.
Wijdenes
J
J
Bouchet
L
L
Gaidano
G
G
Neipel
F
F
Balabanian
K
K
Galanaud
P
P
Couderc
J
J
Emilie
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D019898:Autocrine Communication; D001402:B-Lymphocytes / Q000473:pathology* / Q000637:transplantation / Q000821:virology; D002455:Cell Division; D004195:Disease Models, Animal; D018450:Disease Progression; D019288:Herpesvirus 8, Human / Q000276:immunology / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009500:Neutralization Tests; D011509:Proteoglycans / Q000096:biosynthesis; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis / Q000737:chemistry; D053668:Syndecan-1; D053667:Syndecans; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D019947:Receptors, Interleukin-6; C508241:SDC1 protein, human; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D053667:Syndecans; D016753:Interleukin-10