Airway inflammation and adjuvant effect after repeated airborne exposures to di-(2-ethylhexyl)phthalate and ovalbumin in BALB/c mice.
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.
Larsen
Søren Thor
ST
National Research Centre for the Working Environment, Copenhagen, Denmark. stl@nrcwe.dk
Hansen
Jitka Stilund
JS
Hansen
Erik Wind
EW
Clausen
Per Axel
PA
Nielsen
Gunnar Damgård
GD
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
D000276:Adjuvants, Immunologic; D000336:Aerosols; D016207:Cytokines; D007074:Immunoglobulin G; D010968:Plasticizers; D007073:Immunoglobulin E; D000536:Aluminum Hydroxide; D010047:Ovalbumin; D004051:Diethylhexyl Phthalate