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Interleukin 6 is essential for in vivo development of B lineage neoplasms.

Abstract
Interleukin (IL) 6 has been suggested to be the major cytokine responsible for proliferation of neoplastic plasma cells in both human myeloma and mouse plasmacytoma. Much of the evidence supporting this suggestion is derived from in vitro studies in which the survival or proliferation of some plasma cell tumors has been found to be IL-6 dependent. However, it remains unclear whether this dependency is the consequence of in vivo or in vitro selective pressures that preferentially expand IL-6-responsive tumor cells, or whether it reflects a critical in vivo role for IL-6 in plasma cell neoplasia. To address this question, we have attempted to induce plasma cell tumors in normal mice and in IL-6-deficient mice generated by introduction of a germline-encoded null mutation in the IL-6 gene. The results demonstrate that mice homozygous (+/+) or heterozygous (+/-) for the wild-type IL-6 allele yield the expected incidences of plasma cell tumors. In contrast, mice homozygous for the IL-6-null allele (-/-) are completely resistant to plasma cell tumor development. These studies define the essential role of IL-6 in the development of B lineage tumors in vivo and provide experimental support for continued efforts to modulate this cytokine in the treatment of appropriate human B cell malignancies.
AuthorsD M Hilbert, M Kopf, B A Mock, G Köhler, S Rudikoff
JournalThe Journal of experimental medicine (J Exp Med) Vol. 182 Issue 1 Pg. 243-8 (Jul 01 1995) ISSN: 0022-1007 [Print] United States
PMID7790819 (Publication Type: Journal Article)
Chemical References
  • Interleukin-6
  • Terpenes
  • pristane
Topics
  • Alleles
  • Animals
  • B-Lymphocytes (physiology)
  • Base Sequence
  • Cell Division
  • Cocarcinogenesis
  • Crosses, Genetic
  • Female
  • Flow Cytometry
  • Gammaretrovirus (genetics, physiology)
  • Genetic Predisposition to Disease
  • Genotype
  • In Situ Hybridization
  • Interleukin-6 (deficiency, genetics, physiology)
  • Lymphoma, B-Cell (etiology, physiopathology)
  • Lymphoma, T-Cell (etiology, physiopathology)
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Molecular Sequence Data
  • Multiple Myeloma (etiology, physiopathology)
  • Neoplasm Transplantation
  • Oncogenes
  • Plasmacytoma (etiology, physiopathology)
  • Polymerase Chain Reaction
  • Terpenes (toxicity)
  • Tumor Virus Infections (virology)

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