In Vivo and In Vitro Analysis of IL-10 in the NZB Leukemic Model

Cancer Genomics Proteomics. 2004 Sep-Dec;1(5-6):407-418. Epub 2004 Sep 1.

Abstract

Background: The B-1 malignancy, CLL has been associated with a failure to undergo apoptosis and increased endogenous IL-10 production. This study was undertaken to identify IL-10 effects in the NZB murine model of CLL.

Materials and methods: Antisense IL-10 was employed in vitro and in vivo to decrease IL-10 protein. Following treatment, cells were analyzed for alterations in cell cycle and RNA was studied for alterations in gene expression. Additional in vivo studies employed NZB mice in which the IL-10 gene was deleted.

Results: IL-10 (-/-) knockout NZB mice overwhelmingly failed to develop leukemia. In vitro antisense IL-10 treatment resulted in a G2/M block and apoptosis and in vivo treatment with antisense IL-10 increased the survival of mice. Microarray analysis indicated a significant role for IL-10 in cell cycle regulation via cdc25C up-regulation and decreased p47phox redox activity.

Conclusion: In summary, IL-10 is a critical survival factor for malignant B cells via anti-apoptotic and cell cycle effects.