Endogenous interleukin 6 production in multiple myeloma patients treated with chimeric monoclonal anti-IL6 antibodies indicates the existence of a positive feed-back loop

Journal of Clinical Investigation

Volumn 98, Issue 6, 1996, Pages 1441-1448

  Van Zaanen, H C T ^a,e   Koopmans, R P ^a   Aarden, L A ^b   Rensink, H J A M ^b   Stouthard, J M L ^a   Warnaar, S O ^c   Lokhorst, H M ^d   Van Oers, M H J ^a  

^a ACADEMIC MEDICAL CENTER   (Netherlands)

^b CENTRAL LABORATORY   (Netherlands)

^c Centocor   (Netherlands)

^d Academic Hospital Utrecht   (Netherlands)

^e UNIVERSITY OF AMSTERDAM   (Netherlands)

Author keywords

chimeric monoclonal antibody; interleukin 6 production; multiple myeloma

Indexed keywords

INTERLEUKIN 6; MONOCLONAL ANTIBODY;

ADULT; AGED; ARTICLE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; FEMALE; HUMAN; IMMUNOGENICITY; INFECTION PREVENTION; MALE; MULTIPLE MYELOMA; PATHOGENESIS; POSITIVE FEEDBACK; PRIORITY JOURNAL;

EID: 0029780037     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/JCI118932     Document Type: Article

References (35)

1. Anderson, K., R. Jones, C. Morimoto, P. Leavitt, and B. Barut. 1989. Response patterns of purified myeloma cells to hematopoietic growth factors. Blood. 73:1915-1924.
2. Kawano, M., T. Hirano, T. Matsuda, T. Taga, Y. Horii, K. Iwato, H. Asaoku, B. Tang, H. Tanaka, A. Kuramoto, and T. Kishimoto. 1988. Autocrine generation and requirement of BSF 2/IL6 for human multiple myelomas. Nature (Lond.). 332:83-85.
3. Klein, B., X.G. Zhang, M. Jourdan, J. Content, J. Houssiau, L. Aarden, M. Piechaczyk, and R. Bataille. 1989. Paracrine rather than autocrine regulation of myeloma cell growth and differentiation by IL6. Blood. 73:517-526.
4. Nordan, R., J. Pumphrey, and S. Rudikoff. 1987. Purification and NH2-terminal sequence of a plasmacytoma growth-factor derived from the murine macrophage cell line P388 D1. J. Immunol. 139:813-817.
5. Zhang, X.G., B. Klein, and R. Bataille. 1989. IL6 is a potent myeloma cell growth factor in patients with aggressive MM. Blood. 74:11-13.
6. van Oers, M., H., van Zaanen, and H. Lokhorst. 1993. Interleukin-6, a new target for therapy in multiple myeloma? (review). Ann. Hematol. 66:219-223.
7. Bataille, R., M. Jourdan, X.G. Zhang, and B. Klein. 1989. Serum levels of IL6, a potent myeloma cell growth factor, as a reflect of disease severity in plasma cell dyscrasias. J. Clin. Invest. 84:2008-2011.
8. Klein, B., X.G. Zhang, M. Jourdan, J. Boiron, M. Portier, Z. Lu, J. Wijdenes, J. Brochier, and R. Bataille. 1990. IL6 is the central tumor growth factor in vitro and in vivo in multiple myeloma (review). Eur. Cytokine Net. 1: 193-201.
9. Klein, B., J. Wijdenes, X.G. Zhang, M. Jourdan, J. Boiron, J. Brochier, J. Liautard, M. Merlin, C. Clement, B. Morel-Fournier, Z. Lu, P. Mannoni, J. Sany, and R. Bataille. 1991. Murine anti-interleukin-6 monoclonal antibody therapy for a patient with plasma cell leukemia. Blood. 78:1198-1204.
10. Bataille, R., B. Barlogie, Z. Lu, J. Rossi, T. Lavabre-Bertrand, T. Beck, J. Wijdenes, J. Brochier, and B. Klein. 1995. Biologic effects of anti-interleukin 6 murine monoclonal antibody in advanced multiple myeloma. Blood. 86:685-691.
11. Hoffman, T. 1990. Anticipating, recognizing and preventing hazards associated with in vivo use of monoclonal antibodies: Special considerations related to human anti-mouse antibodies. Cancer Research. (suppl); 50:1049s-1050s.
12. Durie, B., and S. Salmon. 1975. A clinical staging system for multiple myeloma. Cancer. 36:842-854.
13. Brakenhoff, J., M. Hart, E. De Groot, F. Di Padova, and L. Aarden. 1990. Structure-function analysis of human IL6. Epitope mapping of neutralizing monoclonal antibodies with amino- and carboxyl- terminal deletion mutants. J. Immunol. 145:561-568.
14. Ehlers, M., J. Grotzinger, F. de Hon, J. Mullberg, J. Brakenhoff, J. Liu, A. Wollmer, and S. Rose-John. 1994. Identification of two novel regions of human IL-6 responsible for receptor binding and signal transduction. J. Immunol. 153:1744-1751.
15. Aarden, L., E. De Groot, O. Schaap, and P. Lansdorp. 1987. Production of hybridoma growth factor by human monocytes. Eur. J. Immunol. 17:1411-1416.
16. Aarden, L. 1991. Plasmacytomas. In Mechanisms of B Cell Neoplasm. F. Melchens and M. Potter, editors. ER, Basel, Switzerland. 429-433.
17. Metzler, C., and D. Weiner. 1989. PC Nonlin. SCI Software, Lexington. KY.
18. Stouthard, J., J. Romijn, T. van der Poll, E. Endert, S. Klein, P. Bakker, C. Veenhof, and H. Sauerwein. 1995. Endocrinologic and metabolic effects of interleukin-6 in humans. Am. J. Phys. 268:813-819.
19. Hell, M., L. Boeije, E. de Groot, A. de Vos, and L. Aarden. 1991. ELISA for IL6. J. Immunol. Methods. 138:47-56.
20. Klein, B., and H. Brailly. 1995. Cytokine-binding proteins: stimulating antagonists. Immunol. Today. 16:216-220.
21. van Zaanen, H., H. Lokhorst, L. Aarden, I. Rensink, S. Warnaar, and M. van Oers. 1994. Phase I/II multiple-dose pilot study of chimeric monoclonal anti-IL6 antibody in MM. Br. J. Haematol. 87:Suppl.I. 238 (Abstr.).
22. Wintrobe's Clinical Hematology. Ninth ed., 1993. Vol. 1. 450. Lea & Febiger, Philadelphia/London.
23. May, L., R. Neta, L. Moldawer, J. Kenney, K. Patel, and P. Sehgal. 1993. Antibodies chaperone circulating IL-6. Paradoxical effects of anti-IL6 "neutralizing" antibodies in vivo. J. Immunol. 151:3225-3236.
24. Martens, E., C. Dillen, W. Put, H. Heremans, J. Van Damme, and A. Billiau. 1993. Increased circulating interleukin 6 activity in endotoxin- challenged mice pretreated with anti-IL6 antibody is due to IL6 accumulated in antigen-antibody complexes. Eur. J. Immunol. 23:2026-2029.
25. May, L., K. Patel, D. Garcia, M. Ndubuisi, S. Ferrone, A. Mittelman, A. Mackiewicz, and P. Sehgal. 1994. Sustained high levels of circulating chaperoned Interleukin-6 after active specific cancer immunotherapy. Blood. 84:1887-1895.
26. Mihara, M., Y. Koishihara, H. Fukui, K. Yasukawa, and Y. Ohsugi. 1991. Murine anti-human IL6 monoclonal antibody prolongs the half-life time in circulating blood and thus prolongs the bioactivity of human IL6 in mice. Immunology. 74:55-59.
27. Heremans, H., C. Dillen, W. Put, J. Van Damme, and A. Billiau. 1992. Protective effect of anti-IL6 antibody against endotoxin, associated with paradoxically increased IL6 levels. Eur. J. Immunol. 22:2395-2401.
28. Heinrich, P., J. Castell, and T. Andus. 1990. Interleukin-6 and the acute phase response (review). Biochem. J. 265:621-636.
29. Yamazaki, K., T. Taga, Y. Hirata, H. Yawata, Y. Kawanishi, B. Seed, T. Taniguchi, T. Hirano, and T. Kishimoto. Cloning and expression of the human interleukin-6 (BSF-2/IFNβ2) receptor. Science (Wash. DC). 241:825-828.
30. Lu, Z., J. Brochier, J. Wijdenes, H. Brailly, R. Bataille, and B. Klein. 1992. High amounts of circulating IL6 in the form of monomeric immune complexes during anti-IL6 therapy. Towards a new methodology for measuring overall cytokine production in human in vivo. Eur. J. Immunol. 22:2819-2824.
31. Lu, Z., H. Brailly, J. Wijdenes, R. Bataille, J. Rossi, and B. Klein. 1995. Measurement of whole body IL-6 production: prediction of the efficacy of anti-IL-6 treatments. Blood. 86:3123-3131.
32. Castell, J., J. Klapproth, V. Gross, E. Walter, T. Andus, L. Snyers, J. Content, and P. Heinrich. 1990. Fate of interleukin-6 in the rat. Eur. J. Biochem. 189:113-118.
33. Castell, J., T. Geiger, V. Gross, T. Andus, E. Walter, T. Hirano, T. Kishimoto, and P. Heinrich. 1988. Plasma clearance, organ distribution and target cells of interleukin 6/ hepatocyte-stimulating factor in rat. Eur. J. Biochem. 177: 357-361.
34. Tienhaara, A., K. Pulkki, K. Matilla, K. Irjala, and T. Pelliniemi. 1994. Serum immunoreactive IL6 and CRP levels in patients with MM at diagnosis. Br. J. Haematol. 86:391-393.
35. Lokhorst, H., T. Lamme, M. de Smet, S. Klein, R. de Weger, R. van Oers, and A. Bloem. 1994. Primary tumor cells of myeloma patients induce IL6 secretion in long-term bone marrow cultures. Blood. 84:2269-2277.