Local therapy with CpG motifs in a murine model of allergic airway inflammation in IFN-beta knock-out mice.
BACKGROUND
CpG oligodeoxynucleotides (CpG-ODN) are capable of inducing high amounts of type I IFNs with many immunomodulatory properties. Furthermore, type-I IFNs have been proposed to play a key role in mediating effects of CpG-ODN. The precise role of IFN-beta in the immunomodulatory effects of CpG-ODN is not known.


OBJECTIVE
Here, we aimed to elucidate the role of IFN-beta in the anti-allergic effect of CpG motifs.


METHODS
We assessed the immune response in OVA-primed/OVA-challenged IFN-beta knockout (-/-) mice compared to wild type (WT) control, after intranasal and systemic treatment with synthetic CpG motifs.


RESULTS
Vaccination with CpG-ODN reduced the number of cells in airways of OVA-sensitized WT but not IFN-beta-/- mice. Although airway eosinophilia was reduced in both treated groups, they were significantly higher in IFN-beta-/- mice. Other inflammatory cells, such as lymphocytes and macrophages were enhanced in airways by CpG treatment in IFN-beta-/- mice. The ratio of IFN-gamma/IL-4 cytokines in airways was significantly skewed to a Th1 response in WT compared to IFN-beta-/- group. In contrast, IL-4 and IgE were reduced with no differences between groups. Ag-specific T-cell proliferation, Th1-cytokines such as IFN-gamma, IL-2 and also IL-12 were significantly lower in IFN-beta-/- mice. Surprisingly, we discovered that intranasal treatment of mice with CpG-ODN results in mild synovitis particularly in IFN-beta-/- mice.


CONCLUSIONS
Our results indicate that induction of Th1 response by therapy with CpG-ODN is only slightly and partially dependent on IFN-beta, while IFN-beta is not an absolute requirement for suppression of airway eosinophilia and IgE. Furthermore, our finding of mild synovitis is a warning for possible negative effects of CpG-ODN vaccination.
Matheu
Victor
V
Section of Medical Inflammation Research, Department of Cell & Molecular Biology; Lund University; Sweden. Victor.Matheu@inflam.lu.se
Treschow
Alexandra
A
Teige
Ingrid
I
Navikas
Vaidrius
V
Issazadeh-Navikas
Shohreh
S
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D018899:CpG Islands; D016207:Cytokines / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D016899:Interferon-beta / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D010047:Ovalbumin; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000276:immunology* / Q000628:therapy*; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D016899:Interferon-beta; D010047:Ovalbumin