CpG oligodeoxynucleotide protection in polymicrobial sepsis is dependent on interleukin-17.
CpG oligodeoxynucleotides (ODNs) may prevent mortality from infection. We have identified a therapeutic benefit in treating sepsis with phosphorothioate ODN sequences containing the CpG motif. Sepsis was induced in rats by cecal ligation and puncture (CLP), and treatment with CpG ODNs reduced sepsis mortality from 80% to 15% during a 108-h period. Protection from mortality was dose dependent. Bacterial load in peritoneal fluid was reduced in CpG ODN-treated versus non-CpG ODN-treated rats after CLP. Lung injury, as determined by total myeloperoxidase activity, was also reduced in CpG ODN-treated versus non-CpG ODN-treated rats after CLP. Indirect evidence suggests that CpG-induced expression of interleukin (IL)-23 as levels of p40--but not p35--were significantly increased in both plasma and peritoneal lavage fluid in CpG ODN-treated versus non-CpG ODN-treated rats 24 h after CLP. Anti-IL-17 antibody inhibited the CpG-mediated prevention of mortality. These data suggest that IL-17 may mediate CpG-inducible host defenses during intraabdominal sepsis.
Rice
Lauren
L
Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Orlow
Daniel
D
Ceonzo
Katherine
K
Stahl
Gregory L
GL
Tzianabos
Aurthur O
AO
Wada
Hiromi
H
Aird
William C
WC
Buras
Jon A
JA
D000818:Animals; D017209:Apoptosis; D018899:CpG Islands; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D018664:Interleukin-12 / Q000737:chemistry / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology*; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000737:chemistry / Q000276:immunology; D008168:Lung / Q000201:enzymology / Q000473:pathology; D008297:Male; D009838:Oligodeoxyribonucleotides / Q000276:immunology / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D015996:Survival Rate; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology
C408982:CPG-oligonucleotide; C508842:Il23a protein, rat; D020381:Interleukin-17; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D009838:Oligodeoxyribonucleotides; D018664:Interleukin-12; D009195:Peroxidase