Desensitization of ovalbumin-sensitized mice by repeated co-administrations of di-(2-ethylhexyl) phthalate and ovalbumin.
BACKGROUND
The plasticizer di-(2-ethylhexyl) phthalate (DEHP) has been shown to stimulate a non-allergy related immune response with increased levels of IgG1 and IgG2a, but not IgE, after co-administration with the model allergen ovalbumin (OVA) in mice. In mice, decreased IgG1 and increased IgG2a have been associated with the development of mucosal tolerance towards inhaled allergens. As DEHP selectively promote formations of IgG1 and IgG2a without stimulating the IgE response, it was hypothesized that DEHP may suppress an established IgE mediated allergic response. Mice pre-sensitised to OVA were repeatedly co-exposed to DEHP and OVA and the effects were evaluated on the levels of OVA-specific antibodies, ex vivo cytokine levels and the degree of lung inflammation after challenge with an OVA aerosol.


RESULTS
Compared to the OVA-sensitised control mice, multiple co-exposures to DEHP+OVA reduced the IgG1 level and reduced the IgE/IgG2a ratio. This suggests that DEHP may attenuate allergic sensitisation, as the IgE/IgG2a ratio has been shown to correlate with the degree of anaphylaxis. Nevertheless, no effect of DEHP exposures was seen on inflammatory cells in bronchoalveolar lavage fluid and on cytokine levels in spleen cell culture.


CONCLUSIONS
Data from humane and murine studies suggest that DEHP may attenuate the allergic response. More studies are necessary in order to assess the size of this effect and to rule out the underlying mechanism.
Larsen
Søren T
ST
National Research Centre for the Working Environment, Lersø Parkallé 105, DK-2100 Copenhagen Ø, Denmark. stl@nrcwe.dk
Nielsen
Gunnar D
GD