title: Modulation of oligonucleotide-induced immune stimulation by cyclodextrin analogs.
abstract: Some phosphorothioate oligonucleotides have been shown previously to stimulate cell proliferation and immunoglobulin production. In the current study, we examined the effects of cyclodextrin analogs as immunomodulatory agents for oligonucleotide-induced immune stimulation, both in vitro and in vivo. Incubation of splenocytes with a 27-mer phosphorothioate oligonucleotide that induces immune stimulation increased cell proliferation as measured by [3H]thymidine incorporation, whereas treatment of splenocytes with the phosphorothioate oligonucleotide complexed to cyclodextrin analogs markedly reduced oligonucleotide-induced cell proliferation. Similarly, administration of the 27-mer phosphorothioate oligonucleotide into mice resulted in splenomegaly and an increase in IgM production 48 hr post-administration. Administration of the oligonucleotide along with cyclodextrin analogs resulted in a significant suppression of splenomegaly and IgM response. Such suppression was dependent on the concentration of cyclodextrin analogs and was observed with various other immune stimulatory phosphorothioate oligonucleotide sequences. Administration of cyclodextrin analogs alone had no effect on splenomegaly or immune stimulation.
authors.affiliation: Hybridon, Inc., Worcester, MA 01605, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhao
authors.forename: J
authors.initials: J
authors.lastname: Temsamani
authors.forename: P L
authors.initials: PL
authors.lastname: Iadarola
authors.forename: S
authors.initials: S
authors.lastname: Agrawal
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D003505:Cyclodextrins / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D007107:Immune System / Q000187:drug effects*; D007075:Immunoglobulin M / Q000096:biosynthesis; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D009841:Oligonucleotides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013163:Splenomegaly / Q000139:chemically induced; D013936:Thymidine / Q000378:metabolism; D047392:beta-Cyclodextrins
chemical_list: D000276:Adjuvants, Immunologic; D003505:Cyclodextrins; D007075:Immunoglobulin M; D009841:Oligonucleotides; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C059250:2-hydroxyethyl-beta-cyclodextrin; D013936:Thymidine