Document 1084
 DOCN  M9471084
 TI    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).
 DT    9409
 AU    Baiocchi R; Sullivan L; Tan J; Narula S; Caligiuri M; Dept of Medicine,
       Roswell Park Cancer Inst., Buffalo, NY 14263
 SO    Proc Annu Meet Am Soc Clin Oncol; 13:A969 1994. Unique Identifier :
       AIDSLINE ICDB/94600965
 AB    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.
 DE    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
       MEETING ABSTRACT  RANDOMIZED CONTROLLED TRIAL  CLINICAL TRIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).