title: Reducing LPS content in cockroach allergens increases pulmonary cytokine production without increasing inflammation: a randomized laboratory study.
abstract: BACKGROUND
  Endotoxins are ubiquitously present in the environment and constitute a significant component of ambient air. These substances have been shown to modulate the allergic response, however a consensus has yet to be reached whether they attenuate or exacerbate asthmatic responses. The current investigation examined whether reducing the concentration of lipopolysaccharide (LPS) in a house dust extract (HDE) containing high concentrations of both cockroach allergens 1 and LPS would attenuate asthma-like pulmonary inflammation.
  
  
  METHODS
  Mice were sensitized with CRA and challenged with the intact HDE, containing 182 ng of LPS, or an LPS-reduced HDE containing 3 ng LPS, but an equivalent amount of CRA. Multiple parameters of asthma-like pulmonary inflammation were measured.
  
  
  RESULTS
  Compared to HDE challenged mice, the LPS-reduced HDE challenged mice had significantly reduced TNFα levels in the bronchoalveolar lavage fluid. Plasma levels of IgE and IgG1 were significantly reduced, however no change in CRA-specific IgE was detected. In HDE mice, plasma IgG2a levels were similar to naïve mice, while LPS-reduced HDE mice had significantly greater concentrations. Reduced levels of LPS in the HDE did not decrease eosinophil or neutrophil recruitment into the alveolar space. Equivalent inflammatory cell recruitment occurred despite having generally higher pulmonary concentrations of eotaxins and CXC chemokines in the LPS-reduced HDE group. LPS-reduced HDE challenge induced significantly higher concentrations of IFNγ, and IL-5 and IL-13 in the BAL fluid, but did not decrease airways hyperresponsiveness or airway resistance to methacholine challenge.
  
  
  CONCLUSIONS
  These data show that reduction of LPS levels in the HDE does not significantly protect against the severity of asthma-like pulmonary inflammation.
authors.affiliation: Department of Pathology and Laboratory Medicine, Boston University School of Medicine, 670 Albany Street, 720 Harisson Avenue, Boston, MA 02118, USA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Natarajan
authors.forename: Jiyoun
authors.initials: J
authors.lastname: Kim
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Bouchard
authors.forename: William
authors.initials: W
authors.lastname: Cruikshank
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Remick
mesh_terms: D000485:Allergens / Q000378:metabolism*; D000818:Animals; D001249:Asthma / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid; D019743:Chemokines, CXC / Q000378:metabolism; D003058:Cockroaches / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008070:Lipopolysaccharides / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000378:metabolism*; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000485:Allergens; D019743:Chemokines, CXC; D016207:Cytokines; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E