Dietary provocation of reginic allergy in young rats

Abstract

Atopic allergies are common and important causes of childhood morbidity. Treatment for conditions such as eczema, asthma and rhinitis is usually symptomatic and attention has therefore turned to their possible prevention. Though the genetic predisposition to atopic allergies is not in doubt, their provocation by environmental factors, as shown by a number of clinical studies, suggests that non-genetic factors may moderate the expression of atopic symptoms. One such factor is exclusive breast feeding, protecting the human infant against sensitization to several recognized antigens; an antigen non-specific effect. In contrast, other studies have shown that infants fed with cows milk preparations have more atopic disease and more immunoglobulin E antibody (lgE), though many do not produce an lgE response to cows milk proteins. Therefore it is not established from the clinical data whether cows milk feeds themselves provoke allergies, or if removing the protective effect of breast milk results in sensitization. Furthermore, feeding supplements of cows milk to a breast fed baby is a common practice, and its immunological effect is uncertain, though clinical evidence suggests that such a feeding regimen fails to protect against atopic allergies. Jarrett and her colleagues have characterized lgE responses in Hooded Lister rats and this species was chosen for my investigations to determine if supplements of cows milk fed to suckling rat pups modifies the subsequent lgE antibody response to ovalbumin; this antigen non-specific effect was demonstrated. Supplements of a cows milk-based preparation increased the lgE and lgG response to injected ovalbumin. The effect was antigen dose dependent, more evident when a small dose was injected than with a higher dose which produced comparably high lgE responses in both supplemented and unsupplemented animals. In contrast to the effect with the low dose, a higher dose reduced the lgG antiovalbumin response in supplemented rats; the explanation for this is unknown. One suggested mechanism of the antigen non-specific effect of cows milk feeds in human infants is that of disturbance in intestinal bacterial colonization, releasing endotoxin adjuvant into the circulation; my experiments in rats lend some support to this concept. The supplementary feeds with a cows milk preparation did not provoke an antibody response to cows milk proteins, suggesting that the detrimental effects of cows milk feeds are not confined to milk protein antigens; as in human infants, they potentiate sensitization to several recognized antigens. It is clear that such an effect is not just that of removing the protection against atopic allergy afforded by breast milk. Supplementary feeds to suckling rat pups did not influence the previously described antigen specific suppression of lgE response in the offspring of sensitized females; I have shown that suppression results from passive transfer of maternal antibody to the offspring. The relevance of this to human atopic allergy is uncertain and there is, as yet, no evidence that allergic mothers protect their babies against sensitization. The lgE antibody response to immunization regimens previously described for eliciting such responses in adult outbred Hooded Lister rats were studied in the young rat by paper radioallergosorbent test and by passive cutaneous anaphylaxis. The factors which initiate the allergic response in the young rat may well also apply to the origin of atopic allergy in human infants. Allergic rats demonstrate anaphylaxis with intravenous antigen challenge and increased antigen absorption with oral antigen challenge; these effects parallel closely the clinical effects of human reaginic allergy. The results of these studies support the view that dietary supplements fed to suckling mammals have important immunological consequences.