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


CONCLUSIONS
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.
Månsson
A
A
Department of Otorhinolaryngology, Malmö University Hospital, Lund University, Sweden.
Bachar
O
O
Adner
M
M
Cardell
L-O
LO
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000328:Adult; D000485:Allergens / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017817:Nasal Lavage Fluid / Q000276:immunology; D009297:Nasal Mucosa / Q000187:drug effects* / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology*; D012882:Skin Tests; D051217:Toll-Like Receptor 9 / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000485:Allergens; C408982:CPG-oligonucleotide; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9; D009569:Nitric Oxide