title: Tenidap inhibits replication of the human immunodeficiency virus-1 in cultured cells.
abstract: Interleukin-6 (IL-6) may be important in the pathogenesis of HIV-1 because of its ability to induce HIV-1 expression in infected cells in vitro. Tenidap, a structurally and functionally novel antirheumatic drug affecting diverse biologic processes, has been shown to reduce IL-6 production by peripheral blood mononuclear cells stimulated with lipopolysaccharide. Tenidap also inhibits the activity of chloride-bicarbonate exchangers and causes acidification of the cytoplasmic compartment that is similar to the effect of the anion transport inhibitor UK5099. Furthermore, tenidap inhibits the cyclooxygenase-mediated pathway of arachidonic acid metabolism as do the nonsteroidal antiinflammatory drugs (NSAIDs). Here we show that tenidap decreased HIV-1 replication as measured by p24 core antigen in the acutely infected CD4+ T-lymphocyte lines H9 and Jurkat, in the acutely infected monocyte line U937, and in its chronically infected subclone U1.8/HIV. These effects were seen at concentrations in the range of 3 to 15 microM, well below those toxic to cells. The antiviral effects of tenidap may be independent of its ability to reduce IL-6 production based on the observations that these effects were as prominent in IL-6 nonresponsive lines as in IL-6 responsive lines and that the inhibition of p24 production was not reversed by exogenous IL-6.
authors.affiliation: Division of Cell Growth and Regulation, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Dezube
authors.forename: C M
authors.initials: CM
authors.lastname: Ahlers
authors.forename: J P
authors.initials: JP
authors.lastname: Lawrence
authors.forename: E I
authors.initials: EI
authors.lastname: Teng
authors.forename: S L
authors.initials: SL
authors.lastname: Silberman
authors.forename: A B
authors.initials: AB
authors.lastname: Pardee
authors.forename: R W
authors.initials: RW
authors.lastname: Finberg
mesh_terms: D000179:Acrylates / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis; D019169:Jurkat Cells; D007928:Lethal Dose 50; D009000:Monocytes; D000078183:Oxindoles; D010894:Piroxicam / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*; D000093242:Interleukin-6 Inhibitors
chemical_list: D000179:Acrylates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D016655:HIV Core Protein p24; D007211:Indoles; D015850:Interleukin-6; D000078183:Oxindoles; D010894:Piroxicam; D000093242:Interleukin-6 Inhibitors; C043654:2-cyano-3-(1-phenylindol-3-yl)acrylate; C062866:tenidap