Interleukin-18 stimulates HIV-1 replication in a T-cell line

Interleukin-18 (IL-18) is a recently identified proinflammatory cytokine, I ts ability to induce interferon-gamma suggests a potential virustatic effec t. On the other hand, it stimulates NF kappa B - an activator of HIV replic ation. Recently, stimulation of HIV-1 in monocytic cells has been demonstra ted. In the present study, the influence of IL-18 on HIV-1 replication in l ymphatic cells was investigated. Hut78 cells were infected with HIV-1 in th e presence of recombinant human IL-18 expressed either in E. coli or eucary otically by baculovirus in Sf9 cells. HIV-1 replication was monitored by p2 4 ELISA and endpoint titration of culture supernatants on C8166 cells. The addition of IL-18 led to a 3- to 15-fold enhancement of HIV replication in Hut78 cells. By addition of neutralising monoclonal anti-IL-18 antibodies, this effect of IL-18 was reduced by 75%, Exposure of Hut78 to IL-18 prior t o HIV infection could exclude the possibility that IL-18 promotes infection of cells. Taken together, these data provide direct evidence for an IL-18- mediated enhancement of HIV-1 replication in lymphatic cells.