ovalbumin and butylbenzyl-phthalate

During recent decades the prevalence of IgE-mediated (atopic) allergic diseases in Western Europe and the USA has been increasing dramatically. It has been suggested that one possible cause is the presence in the environment of chemicals that may act as adjuvants, enhancing immune and allergic responses. Certain commonly used phthalate plasticizers such as butyl benzyl phthalate (BBP) have been implicated in this way. In the current experiments, the impact of BBP, applied by a physiologically relevant exposure route, on the vigour of immune responses induced in BALB/c strain mice has been examined. Mice were immunized via subcutaneous injection with the reference allergen ovalbumin (OVA) and received concurrent topical treatment with doses of BBP that induced significant changes in liver weight. The generation of specific anti-OVA IgE and IgG1 antibodies was measured by passive cutaneous anaphylaxis and by enzyme-linked immunosorbant assays, respectively. Topical administration of BBP was without impact on anti-OVA IgE antibody responses, regardless of whether BBP was applied locally or distant to the site of OVA immunization. However, same-site treatment with high-dose BBP (100 mg) did result in a modest elevation in anti-OVA IgG1 antibody production, a subclass of antibody used as a surrogate marker of IgE responses. Taken together with human exposure data, these results suggest that the doses of phthalate encountered in the home environment are unlikely to be a major factor contributing to the increased incidence of asthma and allergy in the developed world.

Topics: Adjuvants, Immunologic; Administration, Topical; Allergens; Animals; Dose-Response Relationship, Drug; Environmental Pollutants; Enzyme-Linked Immunosorbent Assay; Female; Immunoglobulin E; Immunoglobulin G; Injections, Intraperitoneal; Liver; Mice; Mice, Inbred BALB C; Organ Size; Ovalbumin; Passive Cutaneous Anaphylaxis; Phthalic Acids; Plasticizers

In a recent study, di-(2-ethylhexyl) phthalate (DEHP) and its metabolite, mono-2-ethylhexyl phthalate, were shown to possess adjuvant effect [Toxicology 169 (2001) 37; Toxicology Letters 125 (2001) 11]. The present study investigates the adjuvant effect of another important commercial phthalate plasticizer, benzyl butyl phthalate (BBP) as well as its degradation products, phthalic acid and benzyl alcohol (BA) in a murine model. The model antigen, ovalbumin (OA), was injected either alone (OA control group), together with one of the test substances (test group) or together with aluminium hydroxide, which served as the positive adjuvant control. The mice were boosted either once or twice with OA before blood was collected and assayed for the content of OA-specific IgE, IgG1 and IgG2a antibodies by ELISA methods. Adjuvant effect was defined as a statistically significant increased antibody level in the test groups compared with the OA control group. Conversely, if the antibody production in a test group was significantly lower than the OA control group, it was deemed to be immunosuppression. This study demonstrated that BBP, in contrast to DEHP, did not possess adjuvant effect. Furthermore, immunosuppression was apparent in the case of BA. The study also demonstrated that if the injections give rise to formation of wounds, it may cause false positive results.

Topics: Adjuvants, Immunologic; Animals; Benzyl Alcohol; Dose-Response Relationship, Immunologic; Enzyme-Linked Immunosorbent Assay; Female; Immunization, Secondary; Immunoglobulin E; Immunoglobulin G; Immunosuppressive Agents; Injections, Subcutaneous; Mice; Mice, Inbred BALB C; Ovalbumin; Phthalic Acids; Random Allocation