       Document 0557
 DOCN  M9610557
 TI    Interleukin-10 enhances human immunodeficiency virus type 1 expression
       in a chronically infected promonocytic cell line (U1) by a tumor
       necrosis factor alpha-independent mechanism.
 DT    9601
 AU    Angel JB; Saget BM; Wang MZ; Wang A; Dinarello CA; Skolnik PR;
       Department of Medicine, Tufts University School of Medicine,; Boston, MA
       02111, USA.
 SO    J Interferon Cytokine Res. 1995 Jun;15(6):575-84. Unique Identifier :
       AIDSLINE MED/96006754
 AB    TNF-alpha enhances HIV-1 replication in acutely and chronically infected
       cells and likely contributes to the wasting associated with the acquired
       immunodeficiency syndrome. Agents that inhibit TNF-alpha activity should
       theoretically delay the progression of disease, and several are
       currently in clinical trials. We hypothesized that IL-10, a cytokine
       that suppresses the gene expression and synthesis of TNF-alpha in
       monocytic cells, might inhibit HIV-1 replication. As expected, IL-10
       suppressed PMA-induced TNF-alpha production in U1 cells; however, when
       U1 cells were cultured in the presence of PMA and increasing doses of
       IL-10, a dose-dependent increase in HIV-1 expression was observed. IL-10
       also enhanced IL-1 beta-, TNF-alpha-, and GM-CSF-induced HIV-1
       expression in U1 cells, and this occurred, at least in part, at the
       level of transcription. We next stimulated cells under conditions of
       TNF-alpha blockade. When PMA-induced TNF-alpha activity and HIV-1
       replication were blocked by the presence of soluble TNF receptors, IL-10
       independently enhanced HIV-1 replication. In contrast, other agents that
       are capable of blocking TNF-alpha synthesis or TNF-alpha activity either
       had no effect (IL-13 and IL-4) or inhibited HIV-1 expression (soluble
       TNF receptors and pentoxifylline) in U1 cells. These data suggest that
       IL-10, while inhibiting TNF-alpha synthesis, has an independent
       mechanism of action that enhances HIV-1 replication. Therefore, IL-10
       may have undesirable effects in HIV-1-infected patients.
 DE    Acquired Immunodeficiency Syndrome/*BLOOD  Cell Line  Drug Synergism
       Granulocyte-Macrophage Colony-Stimulating Factor/PHARMACOLOGY
       Hematopoietic Stem Cells/*DRUG EFFECTS/VIROLOGY  Human
       HIV-1/*PHYSIOLOGY  Interleukin-1/PHARMACOLOGY
       Interleukin-10/*PHARMACOLOGY  Monocytes/*DRUG EFFECTS/VIROLOGY
       Recombinant Proteins/PHARMACOLOGY  Support, U.S. Gov't, P.H.S.
       Tetradecanoylphorbol Acetate/PHARMACOLOGY  Tumor Necrosis
       Factor/*BIOSYNTHESIS  Virus Replication/*PHYSIOLOGY  JOURNAL ARTICLE

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

