Interleukin-18 inhibits human immunodeficiency virus type 1 production in peripheral blood mononuclear cells

Interleukin (IL)-18 is an interferon (IFN)-gamma -inducing factor and contr ibutes to the Th1 immune response. IL-18 added after infection of periphera l blood mononuclear cells (PBMC) with monocyte-tropic human immunodeficienc y virus type 1 (HIV-1) inhibited p24 antigen production by a maximum of 72% . IFN-gamma levels in these cultures were increased, and a significant inve rse relationship between HIV-1 production and IFN-gamma levels was observed . A neutralizing anti-IFN-gamma antibody reversed the IL-18 inhibitory effe ct. Preincubation of PBMC with IL-18 before infection inhibited p24 without additional IL-18 (64%). However, compared with the degree of IL-18 inhibit ion observed after a 4-day culture, no additional IL-18 inhibitory effect w as observed during days 5-13. IL-18 also reduced cell surface expression of the HIV-1 receptor CD4. These results demonstrate that IL-18 inhibited HIV -1 production in PBMC through intermediate IFN-gamma. Furthermore, inhibiti on was present during the early stages of viral infection and was associate d with reduced HIV-1 receptor expression.