Role of IL-6 in promoting growth of human EBV-induced B-cell tumors in severe combined immunodeficient mice.
To investigate the role of IL-6 as a growth factor in EBV-induced B lymphoproliferative disorders in immune-suppressed patients, we analyzed two B cell lines derived from two different patients for IL-6 production, expression of the p80 chain of the IL-6 receptor, and the effects on cell growth in vitro and in vivo of neutralizing mAbs specific for IL-6. One of the cell lines (LCL41) was shown to produce large amounts of IL-6 and to express IL-6 receptors. Its in vitro growth was weakly inhibited by the anti-IL-6 MAb. After inoculation into SCID mice, this cell line provoked human B cell tumors, the growth of which was controlled by the anti-IL-6 mAb. Indeed, four i.v. infusions of 0.1 mg at days 30 to 42 after i.p. inoculation of cells led to complete remission in most mice and long term survival in 40% of cases. In contrast, the other B cell line (LCL48) produced smaller amounts of IL-6; its growth was not inhibited in vitro by the anti-IL-6 Ab and was poorly blocked in vivo in SCID mice (40% of remissions and 20% of long-term survival). In addition, a clone derived in vivo in SCID mice from LCL48 was completely IL-6-independent. These results demonstrate that B cell tumors transformed in vivo by EBV in immune-suppressed patients are heterogeneous with respect to IL-6 requirements for proliferation. An antitumoral effect in some of them can be achieved by neutralizing the IL-6-dependent proliferative loop.
Durandy
A
A
INSERM U 132, Hospital for Sick Children, Paris, France.
Emilie
D
D
Peuchmaur
M
M
Forveille
M
M
Clement
C
C
Wijdenes
J
J
Fischer
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000502:physiology; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D017464:Receptors, Complement 3d / Q000502:physiology; D018123:Receptors, Interleukin / Q000032:analysis; D019947:Receptors, Interleukin-6
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D017464:Receptors, Complement 3d; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6