Thalidomide inhibits the replication of human immunodeficiency virus type 1

Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5974-8. doi: 10.1073/pnas.90.13.5974.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy
  • Acquired Immunodeficiency Syndrome / microbiology
  • Adult
  • Cell Line
  • Female
  • HIV Infections / drug therapy
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / microbiology
  • Male
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / microbiology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / microbiology
  • Thalidomide / pharmacology*
  • Thalidomide / therapeutic use
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics
  • Virus Activation / drug effects
  • Virus Replication / drug effects*

Substances

  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Thalidomide