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-I expression in chronically HIV-l-infected promonocytes (U1 cells). Human mesangial cells constitutively secreted interleukin-6 (IL-6) but not tumor necrosis factor-alpha (TNF-α) into the culture medium, whereas PTEC constitutively secreted both IL-6 and TNF-α. 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-α 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-α antibodies additively reduced coculture HIV-1 expression by 87% (P <0.05). We conclude that renal cell production of IL-6 and TNF-α might provide a potent stimulus for HIV-1 expression in HIV-l-infected monocytes that infiltrate the kidney, and that this may play an important role in the pathogenesis of HIVAN.
Bibliographical noteFunding Information:
This study was supported by National Institutes of Health Grant 1RO1DK49401. Portions of this work were presented at the 29th Annual Meeting of the American Society of Nephrology, New Orleans, LA, November 3–7, 1996. The authors thank Paul Walker, Linda Schuveiller, and Laura Ehrlich for technical assistance in the performance of this study.
- Cytokines and HIV
- HIV in renal cytokines
- Mesangial cells
- Proximal tubular cells