Modulation of airway inflammation by CpG oligodeoxynucleotides in a murine model of asthma.
Asthma has been increasing in industrialized countries. Evidence suggests that asthma is caused by a Th2 immune response to inhaled environmental Ags and that childhood infections protect against this. We have shown that bacterial DNA contains motifs, centered on unmethylated CpG dinucleotides, which induce Th1-type responses. We hypothesized that the Th1 effect of these CpG motifs may oppose the Th2 type allergic response and suggest that this may account for the protective effect of childhood infection against asthma. We examined the effects of CpG-motif oligodeoxynucleotides (CpG ODN) in a murine model of asthma. Airway eosinophilia, Th2 cytokine induction, IgE production, and bronchial hyperreactivity were prevented by coadministration of CpG ODN with the Ag. Significantly, in a previously sensitized mouse, CpG ODN can prevent allergen-induced airway inflammation. These studies suggest that exposure to CpG DNA may protect against asthma.
Kline
J N
JN
Department of Medicine, University of Iowa College of Medicine, Iowa City 52242, USA. joel-kline@uiowa.edu
Waldschmidt
T J
TJ
Businga
T R
TR
Lemish
J E
JE
Weinstock
J V
JV
Thorne
P S
PS
Krieg
A M
AM
D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy; D016207:Cytokines / Q000096:biosynthesis; D015226:Dinucleoside Phosphates; D007073:Immunoglobulin E / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology
D016207:Cytokines; D015226:Dinucleoside Phosphates; D007073:Immunoglobulin E; D009838:Oligodeoxyribonucleotides; C015772:CpG dinucleotide