Endogenous IL-10 is a protective factor in drug resistant AIDS-related lymphoma (ARL) (Meeting abstract).

Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

Endogenous IL-10 is a protective factor in drug resistant AIDS-related lymphoma (ARL) (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 36:A1920 1995. Unique Identifier : AIDSLINE ICDB/95609695
Demidem A; Lam D; Gan XH; Levine A; Salahuddin Z; Bonavida B; Department of Microbiology, UCLA School of Medicine, Los Angeles,; CA 90024

Abstract: The objective of this study is to investigate mechanisms of resistance of ARL. Three EBV+ ARL B cell lines were established in culture. These cell lines are resistant to a variety of cytotoxic agents but IFN-gamma pretreatment renders these cells sensitive to those agents. IFN-gamma downregulated both TNF-alpha and IL-10 secretion and the role of IL-10 in resistance was examined. Pretreatment of ARL with anti-IL-10 serum for 48 hr resulted in the following findings: (a) cell growth inhibition; (b) modifications of surface antigens and receptors expression; and (c) significant sensitization of the tumor cells to various cytotoxic agents (diphtheria toxin, TNF-alpha, CDDP, ADR, and VP16). These above findings were specific for ARL and not for other tumors. The role of IL-10 in protection was confirmed by investigating the effect of treatment of ARL with exogenous IL-10 and their subsequent sensitivity to drugs. Pretreatment of ARL for 48 hr with IL-10 (less than 50 ng/ml) abolished their sensitivity to diphtheria toxin and ADR. These findings also provide a mechanism of the observed IFN-gamma-induced sensitization of ARL to drugs. We suggest that IL-10 may behave like Bcl-2, an anti-apoptotic gene, as cloning and sequence of IL-10 cDNA revealed that this cytokine is very similar to the BCRF-1 gene of EBV and that sequence homology between BCRF-1 and Bcl-2 has been documented.

Keywords: Antineoplastic Agents/*PHARMACOLOGY Cell Survival/*DRUG EFFECTS/GENETICS Gene Expression Regulation, Neoplastic/DRUG EFFECTS Human Interferon Type II/PHARMACOLOGY Interleukin-10/*GENETICS Lymphoma, AIDS-Related/*PATHOLOGY Proto-Oncogene Proteins/GENETICS Viral Proteins/GENETICS ABSTRACT
951230
M95C3236

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