Neural correlates of IgE-mediated food allergy Alexandre Salgado Basso a , Frederico Azevedo Costa Pinto a , Momtchilo Russo b , Luiz Roberto Giorgetti Britto c , Luiz Carlos de Sa ´-Rocha a , Joa ˜o Palermo Neto a, * a Department of Pathology, School of Veterinary Medicine, University of Sa ˜o Paulo, Av. Prof. Dr. Orlando Marques de Paiva, 87, Sa ˜ o Paulo 05508-900, Brazil b Department of Immunology, Institute of Biomedical Sciences, University of Sa ˜o Paulo, Sa ˜o Paulo, Brazil c Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sa ˜o Paulo, Sa ˜o Paulo, Brazil Received 1 April 2003; accepted 23 April 2003 Abstract Although many authors have considered the possibility of a direct interaction between food allergy and behavioral changes, the evidence supporting this hypothesis is elusive. Here, we show that after oral ovalbumin (OVA) challenge, allergic mice present higher levels of anxiety, increased Fos expression in emotionality-related brain areas, and aversion to OVA-containing solution. Moreover, treatment with anti-IgE antibody or induction of oral tolerance abrogate both food aversion and the expression of c-fos in the central nervous system (CNS). Our findings establish a direct relationship between brain function and food allergy, thus creating a solid ground for understanding the etiology of psychological disorders in allergic patients. D 2003 Elsevier B.V. All rights reserved. Keywords: Food allergy; IgE; Emotionality; Psychoneuroimmunology; c-fos; CNS; Psychological disorders 1. Introduction Food allergy and other allergic diseases have emerged as major public health problems due to their dramatic increase over the past two to three decades. It is estimated that approximately 8% of children and 2% of the adult population suffer from food allergy (Sampson, 1999; Sampson and Burks, 1996). Additionally, food-induced anaphylaxis is now the leading single cause of anaphylac- tic reactions treated in hospitals in the USA and UK (Sampson, 2000; Wuthrich and Ballmer-Weber, 2001). Food-induced allergic reactions are responsible for a myr- iad of symptoms involving the skin, gastrointestinal (GI) tract, and airways (Crowe and Perdue, 1992; Sampson, 1999). In the GI tract, mast cell degranulation (triggered by cross-linking of IgE, bound to its high-affinity receptor) results in an augmentation of ion secretion by the epithe- lium and an increase in vascular permeability accompanied by contraction of smooth muscle layers and edema of the mucosa (Bischoff et al., 2000; Yu and Perdue, 2001). This jeopardizes the integrity of the epithelial barrier, thus favoring the penetration of other antigens (Ags) (Bischoff et al., 2000; Yu and Perdue, 2001). Although the cellular and molecular mechanisms underlying food allergy are well understood, little is known about the effect of food allergy on brain function. Some authors have reported an association between food allergy and behavioral changes (Atkins, 1986; Crayton, 1986; Gettis, 1989). Indeed, it has been shown that human patients suffering from food allergy present higher prevalence of trait anxiety and/or depression than nonhealthy controls with lactose intoler- ance and healthy controls (Addolorato et al., 1998). However, in similar studies, other authors have failed to find this association (Pearson et al., 1983; Peveler et al., 1996), arguing that the diagnosis of psychological symp- toms in allergic patients was due to an artifact of referral bias (Peveler et al., 1996). The main argument against allergy-induced psychological symptoms has been the lack of supportive evidence for a direct effect of allergy on neural activity and behavior (Pearson, 1988). In the present study, we investigated whether food allergy could modulate neural activity and behavior. More specifically, we examined c-fos expression in brain areas that are involved in the emotional and affective aspects of adaptive and behavioral responses. For this purpose, a 0165-5728/03/$ - see front matter D 2003 Elsevier B.V. All rights reserved. doi:10.1016/S0165-5728(03)00166-8 * Corresponding author. Tel.: +55-11-30917957; fax: +55-11- 30917829. E-mail address: jpalermo@usp.br (J. Palermo Neto). www.elsevier.com/locate/jneuroim Journal of Neuroimmunology 140 (2003) 69 – 77