Synthetic oligonucleotides as modulators of inflammation.
Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs mimic the immunostimulatory activity of bacterial DNA. CpG ODN directly stimulate human B cells and plasmacytoid dendritic cells, promote the production of Th1 and proinflammatory cytokines, and trigger the maturation/activation of professional APC. CpG ODN are finding use in the treatment of cancer, allergy, and infection. In contrast, ODN containing multiple TTAGGG motifs mimic the immunosuppressive activity of self-DNA, down-regulating the production of proinflammatory and Th1 cytokines. Preclinical studies suggest that "suppressive" ODN may slow or prevent diseases characterized by pathologic immune stimulation, including autoimmunity and septic shock. Extensive studies in animal models suggest that the therapeutic value of CpG and TTAGGG ODN may be optimized by early administration.
Klinman
Dennis
D
National Cancer Institute, Frederick, MD 21702, USA. klinmand@mail.nih.gov
Shirota
Hidekazu
H
Tross
Debra
D
Sato
Takashi
T
Klaschik
Sven
S
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D001327:Autoimmune Diseases / Q000517:prevention & control*; D002470:Cell Survival / Q000187:drug effects; D015226:Dinucleoside Phosphates / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000517:prevention & control*; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D012772:Shock, Septic / Q000517:prevention & control*
D000276:Adjuvants, Immunologic; D015226:Dinucleoside Phosphates; D007166:Immunosuppressive Agents; D009838:Oligodeoxyribonucleotides; C015772:CpG dinucleotide