Tenidap inhibits replication of the human immunodeficiency virus-1 in cultured cells.
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.
Dezube
B J
BJ
Division of Cell Growth and Regulation, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Ahlers
C M
CM
Lawrence
J P
JP
Teng
E I
EI
Silberman
S L
SL
Pardee
A B
AB
Finberg
R W
RW
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
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