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Local therapy with CpG motifs in a murine model of allergic airway inflammation in IFN-beta knock-out mice.

Matheu, Victor LU ; Treschow, Alexandra LU ; Teige, Ingrid LU ; Navikas, Vaidrius and Issazadeh, Shohreh LU (2005) In Respiratory Research 6(1). p.25-25
Abstract
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.... (More)
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. CONCLUSION: 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
IFN-γ, eosinophil, arthritis, synovitis, inflammation, asthma, IFN-β, allergy, CpG motifs, knockout, lung, Th1-response
in
Respiratory Research
volume
6
issue
1
pages
25 - 25
publisher
BioMed Central
external identifiers
  • wos:000227999600001
  • pmid:15748290
  • scopus:25444456375
ISSN
1465-9921
DOI
10.1186/1465-9921-6-25
language
English
LU publication?
yes
id
9f951467-9940-432a-81bb-04bf0f42c466 (old id 135175)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15748290&dopt=Abstract
date added to LUP
2007-07-17 13:59:56
date last changed
2017-10-22 03:57:40
@article{9f951467-9940-432a-81bb-04bf0f42c466,
  abstract     = {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. CONCLUSION: 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.},
  author       = {Matheu, Victor and Treschow, Alexandra and Teige, Ingrid and Navikas, Vaidrius and Issazadeh, Shohreh},
  issn         = {1465-9921},
  keyword      = {IFN-γ,eosinophil,arthritis,synovitis,inflammation,asthma,IFN-β,allergy,CpG motifs,knockout,lung,Th1-response},
  language     = {eng},
  number       = {1},
  pages        = {25--25},
  publisher    = {BioMed Central},
  series       = {Respiratory Research},
  title        = {Local therapy with CpG motifs in a murine model of allergic airway inflammation in IFN-beta knock-out mice.},
  url          = {http://dx.doi.org/10.1186/1465-9921-6-25},
  volume       = {6},
  year         = {2005},
}