TY - JOUR T1 - <em>In Vivo</em> and <em>In Vitro</em> Analysis of IL-10 in the NZB Leukemic Model JF - Cancer Genomics - Proteomics JO - Cancer Genomics Proteomics SP - 407 LP - 418 VL - 1 IS - 5-6 AU - BRIAN A. McCARTHY AU - SIEW YEN CHONG AU - GEORGE PARKER AU - MONIQUE MERAMO AU - MING ZHANG AU - JENNIFER CZARNESKI AU - AMAL MANSOUR AU - ELIZABETH RAVECHE Y1 - 2004/09/01 UR - http://cgp.iiarjournals.org/content/1/5-6/407.abstract N2 - 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. ER -