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

Abstract

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.