INTERLEUKIN-6 IS ESSENTIAL FOR IN-VIVO DEVELOPMENT OF B-LINEAGE NEOPLASMS

Interleukin (LL) 6 has been suggested to be the major cytokine respons ible for proliferation of neoplastic plasma cells in both human myelom a and mouse plasmacytoma. Much of the evidence supporting this suggest ion is derived from in vitro studies in which the survival or prolifer ation 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 viv o 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 homozygou s (+/+)or heterozygous (+/-) for the wild-type IL-6 allele yield the e xpected incidences of plasma cell tumors. In contrast, mice homozygous for the IL-6-null allele (-/-) are completely resistant to plasma cel l tumor development. These studies define the essential role of IL-6 i n the development of B lineage tumors in vivo and provide experimental support for continued efforts to modulate this cytokine in the treatm ent of appropriate human B cell malignancies.