Renal cell cytokine production stimulates HIV-1 expression in chronically HIV-1-infected monocytes

Kidney Int. 1998 Mar;53(3):593-7. doi: 10.1046/j.1523-1755.1998.00789.x.


Renal infiltration of human immunodeficiency virus type 1 (HIV-1)-infected monocytes might play an important role in the development of HIV-associated nephropathy (HIVAN). In the present study, we investigated the effects of cytokines produced by cultured human mesangial cells (HMC) and proximal tubular epithelial cells (PTEC) on HIV-1 expression in chronically HIV-1-infected promonocytes (U1 cells). Human mesangial cells constitutively secreted interleukin-6 (IL-6) but not tumor necrosis factor-alpha (TNF-alpha) into the culture medium, whereas PTEC constitutively secreted both IL-6 and TNF-alpha. Coculture of U1 cells with HMC or PTEC for 72 hours markedly stimulated HIV-1 expression, with the p24 antigen concentration in the coculture supernatants ranging from approximately 200 to 1850 pg/ml. The presence of anti-IL-6 antibody in the coculture medium nearly completely blocked HIV-1 expression in the HMC/U1 cell cocultures (P < 0.05). Anti-IL-6 antibody and anti-TNF-alpha antibody blocked HIV-1 expression in the PTEC/U1 cell cocultures by 40% and 53%, respectively (P < 0.05). Moreover, the combination of anti-IL-6 and anti-TNF-alpha antibodies additively reduced coculture HIV-1 expression by 87% (P < 0.05). We conclude that renal cell production of IL-6 and TNF-alpha might provide a potent stimulus for HIV-1 expression in HIV-1-infected monocytes that infiltrate the kidney, and that this may play an important role in the pathogenesis of HIVAN.

Publication types

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

MeSH terms

  • AIDS-Associated Nephropathy / etiology*
  • AIDS-Associated Nephropathy / virology
  • Cells, Cultured
  • Cytokines / biosynthesis*
  • Epithelial Cells / cytology
  • Epithelial Cells / immunology
  • Glomerular Mesangium / cytology
  • Glomerular Mesangium / immunology
  • HIV-1 / pathogenicity
  • HIV-1 / physiology*
  • Humans
  • Interleukin-6 / biosynthesis
  • Kidney / cytology
  • Kidney / immunology*
  • Kidney / virology
  • Kidney Tubules, Proximal / cytology
  • Kidney Tubules, Proximal / immunology
  • Monocytes / virology*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Virus Replication


  • Cytokines
  • Interleukin-6
  • Tumor Necrosis Factor-alpha