Objective and design: To study the in vitro activity of pentoxifylline (PTX), which may be of benefit in AIDS, on cell proliferation, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma (a type 1 cytokine) and interleukin (IL)-10 (a type 2 cytokine) production, viral replication and CD4+ depletion in acutely HIV-1-infected human T cells.
Methods: T cells were stimulated with anti-CD3 antibody or phytohaemagglutinin (PHA) and infected with HIV-1 in presence or absence of PTX. Cell proliferation, CD4+ cell number, nuclear factor (NF)-kappa B activation, p24 antigen release or lymphokine content of the supernatants were evaluated by [3H]-thymidine incorporation, cytofluorimetry, electrophoretic mobility shift assays and specific enzyme-linked immunosorbent assay, respectively.
Results: In HIV-1-infected T cells, PTX inhibited cell proliferation and p24 release and prevented CD4+ depletion associated with HIV replication. Moreover, PTX reduced TNF-alpha, IFN-gamma and IL-10 production and NF-kappa B activation. PTX inhibited with similar potency IFN-gamma, TNF-alpha and cell proliferation. However, the inhibition of p24 release and specially of IL-10 production required significantly lower doses of PTX. Exogenous addition of IL-2 or TNF-alpha in presence of PTX restore T-cell proliferation and NF-kappa B activation respectively, but did not affect p24 inhibition.
Conclusions: Our data suggest that the inhibitory effect of PTX on HIV replication cannot be satisfactorily explained by the inhibition of NF-kappa B or TNF-alpha. Moreover, PTX cannot be primarily considered as a TNF-alpha inhibitor and has several immunomodulatory and antiviral properties which could be of benefit against HIV-1 at various levels.