title: Systemic up-regulation of TLR4 causes lipopolysaccharide-induced augmentation of nasal cytokine release in allergic rhinitis.
abstract: BACKGROUND
  Allergic rhinitis is a systemic disorder, and it is clinically well recognized that it can be aggravated by infection. Activation of the innate immune system constitutes a critical element in the process. Toll-like receptors (TLRs) comprise a part of the innate immune system, and lipopolysaccharide (LPS)-induced activation of TLR4 represents bacterial-induced interactions in various model systems. The present study examines how TLR2 and TLR4 expression is affected by symptomatic allergic rhinitis, and if LPS added upon allergen affects nasal cytokine release.
  
  
  METHODS
  In patients with pollen-induced allergic rhinitis and healthy non-allergic volunteers, nasal lavage (NAL), peripheral blood and bone marrow were sampled before and during the pollen season. TLR2 and TLR4 expression was determined flow cytometrically. Changes in the TLR receptor expression pattern were evaluated by a nasal challenge with allergen followed by LPS, or vice versa. Symptoms along with cells and cytokines in NAL were analyzed.
  
  
  RESULTS
  TLR4 expression increased in leukocytes in NAL, peripheral blood and bone marrow during symptomatic allergic rhinitis. A similar increase was seen for TLR2 in neutrophils in blood. Nasal challenge with allergen followed by LPS augmented the release of IL-4, IL-5, IL-10, IL-13, IFN-γ and TNF-α.
  
  
  CONCLUSIONS
  A systemic up-regulation of TLR4 in symptomatic allergic rhinitis may explain why LPS preceded by allergen increases nasal cytokine release.
authors.affiliation: Division of ENT Diseases, CLINTEC, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: A-K
authors.initials: AK
authors.lastname: Ekman
authors.forename: R
authors.initials: R
authors.lastname: Virtala
authors.forename: M
authors.initials: M
authors.lastname: Fransson
authors.forename: M
authors.initials: M
authors.lastname: Adner
authors.forename: M
authors.initials: M
authors.lastname: Benson
authors.forename: L
authors.initials: L
authors.lastname: Jansson
authors.forename: L O
authors.initials: LO
authors.lastname: Cardell
mesh_terms: D000485:Allergens / Q000276:immunology; D029662:Betula / Q000276:immunology; D001853:Bone Marrow; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D007962:Leukocytes / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D017817:Nasal Lavage Fluid / Q000166:cytology / Q000276:immunology; D009297:Nasal Mucosa / Q000276:immunology*; D031784:Phleum / Q000276:immunology; D011058:Pollen / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D000485:Allergens; D016207:Cytokines; D008070:Lipopolysaccharides; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4