Inhibition of murine macrophage IL-12 production by natural and synthetic DNA

DNA is a complex macromolecule whose immunological properties vary with seq uence and structure. To determine whether DNA can inhibit immune responses, the effects of mammalian DNA and synthetic phosphodiester (Po) and phospho rothioate (Ps) oligo-nucleotides (ODNs) on IL-12 production were tested usi ng murine macrophages. With bacterial DNA as a stimulant, calf thymus DNA a nd human placenta DNA blocked IL-12 production by splenic and bone marrow m acrophages, A (dG)(30) Po ODN and all single-base Ps 30 mer ODNs were also effective inhibitors, The Ps ODNs also blocked IL-12 production induced by lipopolysaccharide (LPS) and a stimulatory Ps ODN, With the J774 cell line, single-base Ps ODNs inhibited IL-12 production induced by bacterial DNA, L PS, and a stimulatory Pa ODN. Together, these results indicate that DNA has inhibitory properties, suggesting that mammalian DNA could limit immune ac tivation during inflammation and counteract the effects of bacterial DNA, ( C) 2000 Academic Press.