The Immune Paradox in Acute Anorexia Nervosa: A Hypothesis Linking Hyperactivity, Restrained Inflammation, Preserved Innate Defense, and Constrained Adaptive Immunity

Background: Anorexia nervosa (AN) is a severe psycho-metabolic disorder characterized by persistent energy restriction and substantial loss of adipose tissue. Despite profound undernutrition and measurable immune alterations, individuals with acute AN (AN-acute) have been reported to experience fewer clinically evident infections than expected from conventional models of malnutrition. This creates an apparent immune paradox. Scope of Review: Immune findings in AN are heterogeneous, reflecting differences in illness duration, eating-disorder subtype, nutritional severity, and methodology. Furthermore, persistent physical activity, a prominent feature of AN-acute, has received relatively little attention despite its important immunomodulatory effects in healthy individuals. This review presents a hypothesis integrating concepts from exercise physiology and immunometabolism with findings on immune function in AN-acute. Hypothesis: The immune phenotype of AN-acute may reflect selective allocation of limited energy, consistent with immunometabolic principles. It is proposed that severe energy restriction may permit sufficient neutrophil- and macrophage-mediated innate defense to contain pathogens early while constraining the more metabolically demanding activation and expansion of adaptive immunity. At the same time, multiple metabolic and endocrine mechanisms may restrain systemic inflammation, potentially reinforced by repeated contraction-derived IL-6 myokine signaling associated with persistent hyperactivity. Conclusions: This model proposes that preserved innate containment, constrained adaptive escalation, and restrained systemic inflammation interact in AN-acute to reduce the clinical expression of infection. It offers a testable framework linking starvation, hyperactivity, immunometabolism, and immune function.