Interleukin (IL)-4 inhibits phorbol-ester induced HIV-1 expression in chronically infected U1 cells independently from the autocrine effect of endogenous tumour necrosis factor-alpha, IL-1beta, and IL-1 receptor antagonist.

The anti-inflammatory cytokine interleukin 4 (IL-4) has shown both inductive and inhibitory effects on the replication of the human immunodeficiency virus type 1 (HIV-1) in primary CD4+ T cells and mononuclear phagocytes. In this study, IL-4 did not induce virus production, but inhibited phorbol esters (PMA)-stimulated HIV expression in chronically infected promonocytic U1 cells. This effect, however, was not accounted for by a decreased secretion of endogenous TNF-alpha induced by phorbol myristate acetate (PMA). We also observed that PMA upregulated the production of both IL-1beta and of IL-1 receptor antagonist (IL-1ra). IL-4 inhibited the secretion of IL-1beta and strongly increased that of IL-1ra; however, these effects were not responsible of IL-4-mediated inhibition of PMA-induced HIV expression since anti-IL-1ra antibodies did not revert IL-4 mediated suppression. U1 cells were transiently transfected with both wild-type (WT) long terminal repeat (LTR) constructs, or with LTR plasmids containing deletions of either the NF-kappaB or the Sp-1 binding sites. IL-4 inhibited LTR-driven transcription triggered by PMA stimulation of U1 cells, and this effect was dependent upon intact NF-kappaB but not Sp-1 binding sites. Thus, IL-4 may favour a state of microbiological quiescence in infected monocytic cells bypassing the induction of HIV expression mediated by pro-inflammatory cytokines.