MODULATION OF OLIGONUCLEOTIDE-INDUCED IMMUNE STIMULATION BY CYCLODEXTRIN ANALOGS

Some phosphorothioate oligonucleotides have been shown previously to s timulate cell proliferation and immunoglobulin production. In the curr ent study, we examined the effects of cyclodextrin analogs as immunomo dulatory agents for oligonucleotide-induced immune stimulation, both i n vitro and in vivo. Incubation of splenocytes with a 27-mer phosphoro thioate oligonucleotide that induces immune stimulation increased cell proliferation as measured by [H-3]thymidine incorporation, whereas tr eatment of splenocytes with the phosphorothioate oligonucleotide compl exed to cyclodextrin analogs markedly reduced oligonucleotide-induced cell proliferation. Similarly, administration of the 27-mer phosphorot hioate oligonucleotide into mice resulted in splenomegaly and an incre ase in IgM production 48 hr post-administration. Administration of the oligonucleotide along with cyclodextrin analogs resulted in a signifi cant suppression of splenomegaly and IgM response. Such suppression wa s dependent on the concentration of cyclodextrin analogs and was obser ved with various other immune stimulatory phosphorothioate oligonucleo tide sequences. Administration of cyclodextrin analogs alone had no ef fect on splenomegaly or immune stimulation. Copyright (C) 1996 Elsevie r Science Inc.