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Regulation of interleukin-18 by THP-1 monocytoid cells stimulated with HIV-1 and Nef viral protein Volume 16, numéro 3, September 2005

Auteurs
Department of Medical and Surgical Sciences, Section of Clinical Microbiology of Turin University, “Amedeo di Savoia” Hospital, Turin, Italy, Section of Infectious Diseases, General Hospital, 21033 Cittiglio, Varese, Italy

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.