SUMMARYFrom anitnal studies we know that oral administration of T-dependent antigens before sensitization effectively induces systemic immune iinresponsiveness. Such 'oral tolerance" is persistent, dosedependent, antigen-specific and presumably T suppressor cell-mediated. Oral tolerance induction could be an effective way to prevent undesired T cell-mediated immune functions, sueh as playing a role in altograft reaciion, autoimmune and allergic diseases. In the present study allergic eontaet hypersensitivity (ACH) to nickel, currently presenting the most frequent contact allergy in man. was chosen to establish the feasibility of oral prevention of undesired T cell-mediated immunity in man. Potentially tolerizing {oral nickel contacts via orthodontic braces) as well as sensitizing (ear piercing) events were studied retrospectively in 2176 patients attending nine European patch test clinics. Patients were interviewed by means ofa confidential questionnaire. The results show that ear piercing strongly favoured development of nickel ACH. More importantly, patients having had oral contacts with nickel-releasing appliances (dental braces) at an early age, but only if prior lo ear piercing, showed a reduced frequency of nickel hypersensitivity. Frequencies of other hypersensitivities, in particular to fragrance, were not affected. These results support our view that induction of specific systemic immunologic tolerance by timely oral administration of antigens is feasible in man.
Oral administration of nickel-chromium to guinea pigs by way of a fixed occlusal splint, or the incorporation of metallic powder or salts into the pelleted food, did not induce hypersensitivity to these metals. In addition, a subsequent attempt to immunize the pre-treated guinea pigs failed in most animals, whereas non-pre-treated guinea pigs became clearly hypersensitive. These results show that oral administration of nickel and chromium induced a state of (partial) tolerance to both metals.
A prospective study of the development of hand eczema was initiated in 86 junior hairdressers and 217 junior nurses. Data obtained at the start of their apprenticeships are presented. None of the junior apprentices presented with hand eczema, but a history of hand eczema was reported by 22/303 (7%) of the students. Almost half of this group (10/22, 45%) could be classified as atopics. Students without a history of hand eczema showed a similar frequency of atopy (17%) as observed in the general population. History of hand eczema was not related to nickel hypersensitivity, as assessed by patch testing. The incidence of nickel hypersensitivity was high in junior hairdressers (26%), compared to junior nurses (12%). Information as to previous contacts with nickel suggested that development of nickel allergy had been promoted by ear-piercing. A lower incidence of nickel hypersensitivity was observed if this potentially sensitizing event had been proceeded by orthodontic treatment with nickel-containing materials. This phenomenon is discussed in terms of orally-induced tolerance.
Metal alloys used in dentistry may elicit adverse side-effects. Contact allergic reactions to metals released from such alloys are among the most frequently encountered problems. In an earlier study, we observed that oral contacts with nickel or chromium salts did not sensitize, but rather decreased the risk of subsequent sensitization to these metals. In the present study, we focused on chromium allergy and extended our earlier observations by further dose-response studies. In addition, we compared different chromium valencies as to their potential oral tolerogenic effects. Development of immunological tolerance in chromium-fed guinea pigs was demonstrated by their inability to develop chromium hypersensitivity after a subsequent immunization attempt. For these studies, the techniques of immunization and skin testing were first improved. One feeding with a high dose of K2Cr2O7 (containing hexavalent chromium) was effective in full tolerance induction. In contrast, trivalent chromium (CrCl3) induced a distinctly lower degree of tolerance, whereas metallic chromium powder was not detectably tolerogenic after a limited number of feedings. Dose-frequency-response studies with K2Cr2O7 showed that full tolerance could also be induced by an increase in the number of feedings with sub-optimal tolerogenic doses. The present results therefore support our hypothesis that long-lasting oral contact with chromium-releasing metal alloys may ultimately result in strong immune tolerance to this metal in subjects without previous skin contact with it. This view is further supported by recent insights into the unique tolerogenicity of oral, as compared with gastro-intestinal, allergenic contacts.
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