European Cytokine Network
MENURegulation of interleukin-18 by THP-1 monocytoid cells stimulated with HIV-1 and Nef viral protein Volume 16, numéro 3, September 2005
- Mots-clés : IL-18, HIV-1 infection, Nef protein, THP-1 cells
- Page(s) : 186-90
- Année de parution : 2005
Interleukin (IL)-18 is a proinflammatory cytokine that plays an important role in both innate and adaptive immune responses against several infectious pathogens. Relatively little is known about its production in HIV-1 infection, and there are controversial data on the influence of IL-18 on HIV-1 replication in vitro. In this study, we investigated the effect of HIV-1 infection, and challenge with recombinant HIV-1 proteins, on IL-18 production by THP-1 cells. This is a monocytoid cell line spontaneously producing IL-18, and consequently is particularly suitable for the study of HIV-1 effects on this type of cytokine regulation. The results reported here demonstrate a significant reduction in IL-18 secretion during HIV-infection. In fact, low levels of IL-18 were released until 120 h from viral challenge (15 ± 11pg/mL at 24 h and 17 ± 13 at 96 h and < 12.5 at 120 h), whereas IL-18 production by uninfected control cells was 193 ± 104pg/mL and 214 ± 114 pg/mL at 24 h and 120 h respectively. At 168 h of incubation, IL-18 production by infected and uninfected cells was found to be 164 ± 88 pg/mL and 325 ± 101 pg/mL respectively (p = 0.001). Of the following viral proteins: gp 120, p24 and Nef, only the last one induced decreased IL-18 secretion in the supernatants of THP-1 cells. This effect is more evident with the concentrations of 5 –1.25 μg/mL of Nef protein (p < 0.0001). In conclusion, our data show that HIV-1 and its regulatory protein, Nef, are able to down-regulate the release of IL-18, in vitro. These results confirm that a variety of modulating effects on the immune response, induced by HIV-infection, may facilitate progression of HIV-1 infection.