title: Airway inflammation and adjuvant effect after repeated airborne exposures to di-(2-ethylhexyl)phthalate and ovalbumin in BALB/c mice.
abstract: BACKGROUND
  Epidemiological studies have suggested an association between exposure to phthalate plasticizers, including di-(2-ethylhexyl)phthalate (DEHP), and increased prevalence of asthma, rhinitis or wheezing. Furthermore, studies in mice have demonstrated an adjuvant effect from DEHP after parenteral administration with the model allergen ovalbumin (OVA).
  
  
  OBJECTIVE
  Exposures to DEHP were investigated for adjuvant effects and airway inflammation in a mouse inhalation model.
  
  
  METHODS
  BALB/cJ mice were exposed to aerosols of 0.022-13 mg/m(3) DEHP and 0.14 mg/m(3) OVA 5 days/week for 2 weeks and thereafter weekly for 12 weeks. Mice exposed to OVA alone or OVA+Al(OH)(3) served as control groups. Finally, all groups were exposed to a nebulized 1% OVA solution on three consecutive days. Serum, bronchoalveolar lavage (BAL) fluid, and draining lymph nodes were collected 24h later.
  
  
  RESULTS
  In the OVA+Al(OH)(3) group, significantly increased levels of OVA-specific IgE and IgG1 in serum as well as of eosinophils in BAL fluid were observed. DEHP affected OVA-specific IgG1 production in a concentration-dependent manner, whereas little effect was seen on IgE and IgG2a. Dose-dependent increases in inflammatory cells were observed in BAL fluids, leading to significantly higher lymphocyte, neutrophil and eosinophil numbers in the OVA+13 mg/m(3) DEHP group. Ex vivo cytokine secretion by cultures of draining lymph nodes suggested that DEHP has a mixed Th1/Th2 cytokine profile.
  
  
  CONCLUSIONS
  Airborne DEHP is able to increase serum IgG1 and lung inflammatory cell levels, but only at very high concentrations. Realistic DEHP levels do not have an adjuvant effect or induce allergic lung inflammation in the present mouse model.
authors.affiliation: National Research Centre for the Working Environment, Copenhagen, Denmark. stl@nrcwe.dk
authors.forename: Søren Thor
authors.initials: ST
authors.lastname: Larsen
authors.forename: Jitka Stilund
authors.initials: JS
authors.lastname: Hansen
authors.forename: Erik Wind
authors.initials: EW
authors.lastname: Hansen
authors.forename: Per Axel
authors.initials: PA
authors.lastname: Clausen
authors.forename: Gunnar Damgård
authors.initials: GD
authors.lastname: Nielsen
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000633:toxicity*; D000336:Aerosols; D000536:Aluminum Hydroxide; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004051:Diethylhexyl Phthalate / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019570:Inhalation Exposure; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects; D010047:Ovalbumin; D010968:Plasticizers / Q000008:administration & dosage / Q000633:toxicity*; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018570:Risk Assessment
chemical_list: D000276:Adjuvants, Immunologic; D000336:Aerosols; D016207:Cytokines; D007074:Immunoglobulin G; D010968:Plasticizers; D007073:Immunoglobulin E; D000536:Aluminum Hydroxide; D010047:Ovalbumin; D004051:Diethylhexyl Phthalate