SUMMARYPrevious work has indicated that the dermis and epidermis of skin contains abundant nerve ®bres closely associated with Langerhans' cells. We have investigated whether these nerve endings are necessary for inducing and evoking a contact sensitivity (CS) response. Topical application of a general or a peptide (calcitonin gene-related peptide and substance P)-speci®c neurotoxin was employed to destroy the nerve ®bres at skin sites subsequently used to induce or evoke the CS response. Elimination of nerve ®bres abolished both induction and effector stages of the speci®c CS response. Denervation did not destroy the local Langerhans' cells, which were observed in increased numbers, or prevent them from migrating to lymph nodes. The local CS response was also abolished by systemic deletion of capsaicin-sensitive nerve ®bres, suggesting that the loss of response was not non-speci®c but associated with the loss of speci®c nerve ®bres. The results indicate that peptidergic nerve ®bres are required to elicit a CS response and may be vital to the normal function of the immune system.

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Assessment of the potential allergenicity (IgE-inducing properties) of novel proteins is an important challenge in the overall safety assessment of foods. Resistance to digestion with pepsin is commonly measured to characterize allergenicity, although the association is not absolute. We have previously shown that specific IgE antibody production induced by systemic [intraperitoneal (i.p.)] exposure of BALB/c strain mice to a range of proteins correlates with allergenic potential for known allergens. The purpose of the present study was to explore further the utility of these approaches using the food allergen, actinidin. Recently, kiwifruit has become an important allergenic foodstuff, coincident with its increased consumption, particularly as a weaning food. The ability of the kiwifruit allergen actinidin to stimulate antibody responses has been compared with the reference allergen ovalbumin, and with the non-allergen bovine haemoglobin. Haemoglobin was rapidly digested by pepsin whereas actinidin was resistant unless subjected to prior chemical reduction (reflecting intracellular digestion conditions). Haemoglobin stimulated detectable IgG antibody production at relatively high doses (10%), but failed to provoke detectable IgE. In contrast, actinidin was both immunogenic and allergenic at relatively low doses (0.25% to 1%). Vigorous IgG and IgG1 antibody and high titre IgE antibody responses were recorded, similar to those provoked by ovalbumin. Thus, actinidin displays a marked ability to provoke IgE, consistent with allergenic potential. These data provide further encouragement that in tandem with analysis of pepsin stability, the induction of IgE after systemic exposure of BALB/c strain mice provides a useful approach for the prospective identification of protein allergens.

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.