Human immunodeficiency virus type 1 infection modulates the interleukin (IL)-1 beta and IL-6 responses of human macrophages to CD40 ligand stimulation

Better understanding of the mechanisms of proinflammatory cytokine producti on during human immunodeficiency virus (HIV) type 1 infection is of pivotal importance. The effect of HIV-1 infection on recombinant CD40 Ligand (CD40 L)-induced interleukin (IL)-1 beta and IL 6 production by human macrophages was analyzed. ELISA and cytofluorometric analysis demonstrated that CD40L stimulation of HIV-1-infected macrophages resulted in substantial productio n of IL-1 beta and IL-6. In contrast, no cytokine response was observed in uninfected cells. No modulation of the receptor for CD40 was found to accou nt for the enhanced response to CD40L. The CD40L effect was not due to lipo polysaccharide contamination and was completely abrogated by preincubation with a monoclonal anti-CD40L antibody. mRNA studies indicated that the prim ing effect of HIV-1 on the macrophage response to CD40L was regulated at th e transcriptional level. Finally, the effect of HIV-1 on the cytokine respo nse could not be abolished by the HIV-1 protease inhibitor U75875 at concen trations that completely suppressed HIV-1 replication.