Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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Originally published online as doi:10.1189/jlb.1107775 on April 22, 2008

Published online before print April 22, 2008
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(Journal of Leukocyte Biology. 2008;84:958-964.)
© 2008 by Society for Leukocyte Biology

Synthetic oligonucleotides as modulators of inflammation

Dennis Klinman1, Hidekazu Shirota, Debra Tross, Takashi Sato and Sven Klaschik

National Cancer Institute, Cancer and Inflammation Program, Frederick, Maryland, USA

1 Correspondence: NCI, Bldg. 567, Rm. 205, Frederick, MD 21702, USA. E-mail: klinmand{at}mail.nih.gov

ABSTRACT

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.

Key Words: CpG • suppressive • ODN • cancer • therapy






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