Peripheral and central dysregulation of innate and adaptive immunity in anorexia nervosa: evidence from a preclinical model

Anorexia nervosa (AN) is a life-threatening psychiatric disorder with a severe multiorgan impact. AN mainly affects young females, and despite it shows a clear symptomatology its etiology is unknown. The combination of severe dieting and hyperactivity, i.e. AN core symptoms, is known to trigger immune system dysregulation of both systemic and central origin. Moreover, because of the increased risk, recurrence, and severity of infections in anorexic patients, the hypothesis that immune system may contribute to AN severity, chronicity and relapse has emerged. To test this, we employed the gold-standard preclinical model of AN, the activity-based anorexia (ABA), that consists of exposing adolescent female rats to food restriction and exercise, thus inducing body weight loss and hyperactivity. In the acute phase, ABA rats showed decreased circulating CD45+ cells and a shift between B cells and granulocytes in the pool of total immune cells in the bone marrow, suggesting an unbalance between innate and adaptive immunity that persist even after body weight recovery. Given the bidirectional nature of the interaction between the immune system and the hypothalamus-pituitary-adrenal axis, we measured corticosterone plasma levels, and glucocorticoid receptor activation in ABA rats hippocampus, that we found increased in the acute phase, while reduced after recovery. These results prompt us to speculate that alterations in the medullary skewing of the innate immune arm occurs because of the acute manifestation of ABA, that in turn may cause severe and endurable dysfunctions also at central level, thus linking the pathological AN phenotype to the immune system dysregulation. Sponsored by Cariplo Foundation 2023-1003