Thalidomide inhibits the replication of human immunodeficiency virus type 1.
Thalidomide, a selective inhibitor of tumor necrosis factor alpha (TNF-alpha) synthesis, suppresses the activation of latent human immunodeficiency virus type 1 (HIV-1) in a monocytoid (U1) line. The inhibition is dose dependent and occurs after exposure of the cells to recombinant TNF-alpha, phorbol myristate acetate, lipopolysaccharide, and other cytokine combinations. Associated with HIV-1 inhibition is a reduction in agonist-induced TNF-alpha protein and mRNA production. Thalidomide inhibition of virus replication in the phorbol myristate acetate- and recombinant TNF-alpha-stimulated T-cell line ACH-2 is not observed. The presence of thalidomide also inhibits the activation of virus in the peripheral blood mononuclear cells of 16 out of 17 patients with advanced HIV-1 infection and AIDS. These results suggest the use of thalidomide in a clinical setting to inhibit both virus replication and the TNF-alpha-induced systemic toxicity of HIV-1 and opportunistic infections.
Makonkawkeyoon
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S
Rockefeller University, New York, NY 10021.
Limson-Pobre
R N
RN
Moreira
A L
AL
Schauf
V
V
Kaplan
G
G
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000382:microbiology; D000328:Adult; D002460:Cell Line; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000382:microbiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000382:microbiology; D013792:Thalidomide / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D014775:Virus Activation / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide