Structure-activity relationship of immunostimulatory effects of phthalates

<p>Abstract</p> <p>Background</p> <p>Some chemicals, including some phthalate plasticizers, have been shown to have an adjuvant effect in mice. However, an adjuvant effect, defined as an inherent ability to stimulate the humoral immune response, was only observed after exposure to a limited number of the phthalates. An adjuvant effect may be due to the structure or physicochemical characteristics of the molecule. The scope of this study was to investigate which molecular characteristics that determine the observed adjuvant effect of the most widely used phthalate plasticizer, the di-(2-ethylhexyl) phthalate (DEHP), which is documented as having a strong adjuvant effect. To do so, a series of nine lipophilic compounds with structural and physicochemical relations to DEHP were investigated.</p> <p>Results</p> <p>Adjuvant effect of phthalates and related compounds were restricted to the IgG1 antibody formation. No effect was seen on IgE. It appears that lipophilicity plays a crucial role, but lipophilicity does not <it>per se </it>cause an adjuvant effect. In addition to lipophilicity, a phthalate must also possess specific stereochemical characteristics in order for it to have adjuvant effect.</p> <p>Conclusion</p> <p>The adjuvant effect of phthalates are highly influenced by both stereochemical and physico-chemical properties. This knowledge may be used in the rational development of plasticizers without adjuvant effect as well as in the design of new immunological adjuvants.</p

Desensitization of ovalbumin-sensitized mice by repeated co-administrations of di-(2-ethylhexyl) phthalate and ovalbumin

<p>Abstract</p> <p>Background</p> <p>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, <it>ex vivo </it>cytokine levels and the degree of lung inflammation after challenge with an OVA aerosol.</p> <p>Findings</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

Structural Parameters and Dynamical Masses for Globular Clusters in M33

Using high-dispersion spectra from the HIRES echelle spectrograph on the Keck I telescope, we measure velocity dispersions for 4 globular clusters in M33. Combining the velocity dispersions with integrated photometry and structural parameters derived from King-Michie model fits to WFPC2 images, we obtain mass-to-light ratios for the clusters. The mean value is M/LV = 1.53 +/- 0.18, very similar to the M/LV of Milky Way and M31 globular clusters. The M33 clusters also fit very well onto the fundamental plane and binding energy - luminosity relations derived for Milky Way GCs. Dynamically and structurally, the four M33 clusters studied here appear virtually identical to Milky Way and M31 GCs.Comment: 25 pages, including 7 figures and 4 tables. Accepted for AJ, Nov 200