Conflito neuro-imunológico na alergia alimentar: entre a aversão e a recompensa?

Abstract

Food allergy is an abnormal immune response to antigens present in the diet. Food allergy to cow's milk is quite frequent, especially in children. Among the allergens present in milk, β- lactoglobulin (BLG) is the most immunogenic. Allergic individuals tend to be more anxious, hypervigilant and it has been described that they have aversion to the consumption of the allergen. In mice, food allergy to the egg white protein ovalbumin is also accompanied by the phenomenon of aversion. To study aversion and its neuroimmune correlates in an experimental food allergy model to BLG, BALB/c mice were sensitized intraperitoneally with BLG and challenged orally with BLG containing solution. We observed that mice sensitized and challenged orally had high levels of BLG specific IgE, however, allergic mice developed only partial aversion to the BLG-containing solution. When mice were given the option of consuming the solution containing the allergen or only water, although they were sensitized and with high levels of serum IgE, they chose to ingest the allergen-containing solution. To elucidate the behavioral processes involved in BLG consumption or aversion, we used a Zero maze test and we observed that the non-sensitized mice that only ingested the BLG-containing solution for 7 days spent more time in the open arms of the labyrinth when compared to the other groups suggesting an exploratory behavior compatible with low levels of anxiety. Analysis of activation of the anxiety-related brain areas by c-Fos expression by neurons of the hypothalamus paraventricular nucleus (PVN) showed that mice drinking BLG-containing solution, sensitized or not to BLG, had lower levels of c-Fos when compared to its controls that did not drink BLG and, therefore, less activation of this region. It is likely that the BLG- containing solution has some anxiolytic effect that conflicts with the aversive effect produced by allergic sensitization to the allergen. The preference for solutions containing BLG is clear in non-sensitized mice that, in contrast to the option to ingest other solutions, chose those containing BLG. The direct effect of BLG on aversion was tested in a classical model of food allergy model to ovalbumin (OVA) in which OVA-sensitized mice were given a solution mixed with OVA and BLG. Surprisingly, addition of BLG into the blend decreased the OVA aversion. Our working hypothesis is that BLG intake activates brain areas of the reward system and, in face of the conflict between aversion and reward, the reward prevails.