Activation of the formyl peptide receptor by the HIV-derived peptide T-20 suppresses interleukin-12 p70 production by human monocytes

It has been proposed that in the early stages of human immunodeficiency (HI V) infection, before the loss of CD4(+) T cells, inhibition of IL-12 produc tion from host antigen-presenting cells plays a critical role in the suppre ssion of T-helper cell type 1 responses. Activation of the G(i)-protein-cou pled high-affinity N-formyl peptide receptor by f-met-leu-phe and HIV-deriv ed peptide T-20-suppressed IL-12 p70 production from human monocytes in res ponse to both T-cell-dependent and T-cell-independent stimulation are repor ted. Activation of the low-affinity N-formyl peptide receptor by the HIV-de rived F-peptide suppressed IL-12 production more modestly. This suppression was pertussis toxin sensitive and was selective for IL-12; the production of IL-10, transforming growth factor-p, and tumor necrosis factor-alpha was unaltered. The production of IL-12 p70 by dendritic cells was unaffected b y these peptides despite functional expression of the high-affinity fMLP re ceptor. These findings provide a potential direct mechanism for HIV-mediate d suppression of IL-12 production and suggest a broader role for G-protein- coupled receptors in the regulation of Innate immune responses. (Blood, 200 1;97:3531-3536) (C) 2001 by The American Society of Hematology.