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Nasal CpG oligodeoxynucleotide administration induces a local inflammatory response in nonallergic individuals.

Månsson, Anne LU ; Bachar, Ofir LU ; Adner, Mikael LU and Cardell, Lars-Olaf LU (2009) In Allergy 64. p.1292-1300
Abstract
Background: We have previously demonstrated the presence of toll-like receptor 9 in the nasal mucosa of both healthy and allergic individuals. CpG motifs, found in bacterial and viral DNA, elicit strong immunostimulatory effects via this receptor. CpG is known to skew the immune system towards a T helper 1 (Th1) profile, thereby suppressing Th2-driven allergic responses. This study was designed to examine the effects of CpG administration in the human nose. Methods: Twenty subjects, of whom 10 suffered from seasonal allergic rhinitis (AR), were challenged intranasally with CpG outside pollen season. Symptom scores, nasal airway resistance (NAR), and nasal and pulmonary nitric oxide (NO) levels were assayed prior to challenge and 30 min, 6,... (More)
Background: We have previously demonstrated the presence of toll-like receptor 9 in the nasal mucosa of both healthy and allergic individuals. CpG motifs, found in bacterial and viral DNA, elicit strong immunostimulatory effects via this receptor. CpG is known to skew the immune system towards a T helper 1 (Th1) profile, thereby suppressing Th2-driven allergic responses. This study was designed to examine the effects of CpG administration in the human nose. Methods: Twenty subjects, of whom 10 suffered from seasonal allergic rhinitis (AR), were challenged intranasally with CpG outside pollen season. Symptom scores, nasal airway resistance (NAR), and nasal and pulmonary nitric oxide (NO) levels were assayed prior to challenge and 30 min, 6, 24 and 48 h post challenge. The presence of leukocytes and various cytokines were analyzed in nasal lavage (NAL) fluids before and after CpG exposure. Results: Increased NAR, nasal NO production and secretion of interleukin (IL)-1beta, IL-6, and IL-8 were seen after CpG exposure. Further analysis revealed that this inflammatory response was more marked in healthy subjects than among patients with AR, although a higher basal inflammatory response was recorded in the allergic group. In vitro experiments suggest that the effects induced by CpG are mediated by epithelial cells and neutrophils. Conclusion: Nasal administration of CpG induces a local airway inflammation, more distinct among healthy than allergic individuals. The reduced responsiveness to CpG in allergic patients might be related to the ongoing minimal persistent inflammation. Results from cytokine analyses reflect the ability of CpG to induce a pro-inflammatory Th1-like immune response. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Allergy
volume
64
pages
1292 - 1300
publisher
Wiley-Blackwell
external identifiers
  • wos:000268968700007
  • pmid:19243360
  • scopus:68949211374
ISSN
1398-9995
DOI
10.1111/j.1398-9995.2009.02012.x
language
English
LU publication?
yes
id
d39da1b4-68aa-48a5-8513-5d7de8f540ea (old id 1302177)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19243360?dopt=Abstract
date added to LUP
2009-03-09 13:24:24
date last changed
2017-01-08 05:30:21
@article{d39da1b4-68aa-48a5-8513-5d7de8f540ea,
  abstract     = {Background: We have previously demonstrated the presence of toll-like receptor 9 in the nasal mucosa of both healthy and allergic individuals. CpG motifs, found in bacterial and viral DNA, elicit strong immunostimulatory effects via this receptor. CpG is known to skew the immune system towards a T helper 1 (Th1) profile, thereby suppressing Th2-driven allergic responses. This study was designed to examine the effects of CpG administration in the human nose. Methods: Twenty subjects, of whom 10 suffered from seasonal allergic rhinitis (AR), were challenged intranasally with CpG outside pollen season. Symptom scores, nasal airway resistance (NAR), and nasal and pulmonary nitric oxide (NO) levels were assayed prior to challenge and 30 min, 6, 24 and 48 h post challenge. The presence of leukocytes and various cytokines were analyzed in nasal lavage (NAL) fluids before and after CpG exposure. Results: Increased NAR, nasal NO production and secretion of interleukin (IL)-1beta, IL-6, and IL-8 were seen after CpG exposure. Further analysis revealed that this inflammatory response was more marked in healthy subjects than among patients with AR, although a higher basal inflammatory response was recorded in the allergic group. In vitro experiments suggest that the effects induced by CpG are mediated by epithelial cells and neutrophils. Conclusion: Nasal administration of CpG induces a local airway inflammation, more distinct among healthy than allergic individuals. The reduced responsiveness to CpG in allergic patients might be related to the ongoing minimal persistent inflammation. Results from cytokine analyses reflect the ability of CpG to induce a pro-inflammatory Th1-like immune response.},
  author       = {Månsson, Anne and Bachar, Ofir and Adner, Mikael and Cardell, Lars-Olaf},
  issn         = {1398-9995},
  language     = {eng},
  pages        = {1292--1300},
  publisher    = {Wiley-Blackwell},
  series       = {Allergy},
  title        = {Nasal CpG oligodeoxynucleotide administration induces a local inflammatory response in nonallergic individuals.},
  url          = {http://dx.doi.org/10.1111/j.1398-9995.2009.02012.x},
  volume       = {64},
  year         = {2009},
}