Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
Epstein-barr virus-associated lymphoproliferative disease (EBV-LPD) in the severe combined immune deficient human/mouse model: prevention with low dose interleukin-2 suppresses production of human interleukin-6 and interleukin-10 (Meeting abstract).
Proc Annu Meet Am Soc Clin Oncol; 13:A969 1994. Unique Identifier : AIDSLINE ICDB/94600965 Baiocchi R; Sullivan L; Tan J; Narula S; Caligiuri M; Dept of Medicine, Roswell Park Cancer Inst., Buffalo, NY 14263
Abstract:
When severe combined immune deficient (SCID) mice are reconstituted with human PBL (hu-PBL-SCID) from individuals seropositive for Epstein-Barr virus (EBV), a fatal EBV-associated lymphoproliferative disease (EBV-LPD) of human B cell origin develops in the majority of the hu-PBL-SCID mice. These EBV-LPD tumors have a surface phenotype and karyotype which bear striking resemblance to EBV-LPD seen in organ transplant recipients and HIV infection. Thus, the hu-PBL-SCID mouse model shows promise for understanding both the pathogenesis and treatment of EBV-induced lymphomagenesis in immunocompromised individuals. In a randomized placebo-controlled study, we recently demonstrated that daily subcutaneous administration of low dose IL-2 can prevent the development of EBV-LPD in the hu-PBL-SCID mouse (Baiocchi and Caligiuri, Blood, 82 Suppl 1;385a). 80% of mice treated with placebo died of EBV-LPD while 22% of rIL-2-treated mice died of EBV-LPD (p=0.0008). In the present report, we characterize the production of two human cytokines, interleukin-10 (huIL-10) and interleukin-6 (huIL-6), in placebo- and IL-2-treated hu-PBL-SCID mice. Tumor bearing animals had strikingly elevated serum concentrations of huIL-10 and huIL-6 while those without tumor had low or undetectable levels (p less than or equal to 0.005 for both cytokines). Northern analysis of RNA isolated from 11 EBV-LPD tumors revealed that 91% (10/11) of tumors expressed huIL-10 ligand mRNA and 82% expressed mRNA for huIL-10 receptor (huIL-10R). The presence of a functional huIL-10R on fresh tumor specimens was confirmed through radiolabeled IL-10 binding studies. These results suggest that production of huIL-10 and huIL-6 may be important in the pathogenesis of EBV-LPD in the hu-PBL-SCID model, and that IL-2 may prevent EBV-LPD through counter-regulation of B cell stimulatory cytokine production. Studies utilizing neutralizing antibodies to huIL-10 and huIL-6 in the absence of IL-2 therapy are underway.
Keywords: Animal Blotting, Northern Comparative Study Herpesviridae Infections/*IMMUNOLOGY/MICROBIOLOGY/*PREVENTION & CONTROL *Herpesvirus 4, Human/ISOLATION & PURIF Human Interleukin-10/*BIOSYNTHESIS Interleukin-2/*THERAPEUTIC USE Interleukin-6/*BIOSYNTHESIS Lymphoproliferative Disorders/*IMMUNOLOGY/MICROBIOLOGY/ *PREVENTION & CONTROL Mice Mice, SCID RNA, Messenger/ANALYSIS RNA, Viral/ANALYSIS ABSTRACT RANDOMIZED CONTROLLED TRIAL CLINICAL TRIAL
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Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
