Adjuvant effects of inhaled mono-2-ethylhexyl phthalate in BALB/cJ mice.

Abstract

Phthalates, including di(2-ethylhexyl) phthalate (DEHP), are widely used and have been linked with the development of wheezing and asthma. The main metabolite of DEHP, mono-2-ethylhexyl phthalate (MEHP), was investigated for adjuvant effects in a mouse inhalation model. BALB/cJ mice were exposed to aerosols of 0.03 or 0.4 mg/m(3) MEHP 5 days/week for 2 weeks and thereafter weekly for 12 weeks together with a low dose of ovalbumin (OVA) as a model allergen. Mice exposed to OVA alone or OVA+Al(OH)(3) served as negative and positive controls, respectively. Finally, all groups were exposed to a nebulized 1% OVA solution on 3 consecutive days to investigate the development of an inflammatory response. Serum, bronchoalveolar lavage (BAL) fluid, and draining lymph nodes were collected 24h later. 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. OVA-specific IgG1 production in both MEHP groups was significantly increased. OVA-specific IgE and IgG2a were not increased significantly. A dose-dependent increase in inflammatory cells was observed in BAL fluid, leading to significantly higher lymphocyte and eosinophil numbers in the OVA+0.4 mg/m(3) MEHP group. Ex vivo cytokine secretion by cultures of draining lymph nodes suggested a T(H)2 profile of MEHP. In conclusion, MEHP acted as a T(H)2 adjuvant after inhalation. However, it is suggested that the inflammation in the MEHP groups was primarily mediated by an IgG1-dependent mechanism. To address implications for humans, a margin-of-exposure was estimated based on the lack of significant effects on IgE production and inflammation after exposures to 0.03 mg/m(3) MEHP observed in the present study and estimated human exposure levels.

• Authors: Jitka Stilund Hansen, Søren Thor Larsen, Lars K Poulsen, Gunnar Damgård Nielsen
• Journal: Toxicology (Toxicology) Vol. 232 Issue 1-2 Pg. 79-88 (Mar 22 2007) ISSN: 0300-483X [Print] Ireland
• PMID: 17241728 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Allergens
• Immunoglobulin G
• Interleukins
• Immunoglobulin E
• Interferon-gamma
• Ovalbumin
• Diethylhexyl Phthalate
• mono-(2-ethylhexyl)phthalate

Topics

• Adjuvants, Immunologic (administration & dosage, toxicity)
• Administration, Inhalation
• Allergens (administration & dosage, toxicity)
• Animals
• Bronchoalveolar Lavage Fluid (cytology)
• Diethylhexyl Phthalate (administration & dosage, analogs & derivatives, immunology, toxicity)
• Female
• Immunoglobulin E (biosynthesis, blood, immunology)
• Immunoglobulin G (blood)
• Inflammation (chemically induced, immunology)
• Interferon-gamma (immunology)
• Interleukins (immunology)
• Lymph Nodes (drug effects, immunology)
• Mice
• Mice, Inbred BALB C
• Ovalbumin (administration & dosage, immunology)
• Respiration (drug effects)
• Respiratory Function Tests