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 contributes to the Th1 immune response. IL-18 added after infection of peripheral blood mononuclear cells (PBMC) with monocyte-tropic human immunodeficiency 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 inverse relationship between HIV-1 production and IFN-gamma levels was observed. A neutralizing anti-IFN-gamma antibody reversed the IL-18 inhibitory effect. Preincubation of PBMC with IL-18 before infection inhibited p24 without additional IL-18 (64%). However, compared with the degree of IL-18 inhibition observed after a 4-day culture, no additional IL-18 inhibitory effect was 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, inhibition was present during the early stages of viral infection and was associated with reduced HIV-1 receptor expression.
Choi
H J
HJ
Department of Medicine, Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, Colorado, USA. hee-jung.choi@uchsc.edu
Dinarello
C A
CA
Shapiro
L
L
D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D016655:HIV Core Protein p24 / Q000378:metabolism; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D020382:Interleukin-18 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000821:virology*
D015704:CD4 Antigens; D016655:HIV Core Protein p24; D020382:Interleukin-18; D007371:Interferon-gamma