# Cytokines and adolescent anorexia nervosa: a case-control study

## TL;DR

This study found that adolescents with early-stage anorexia nervosa have higher levels of certain pro-inflammatory cytokines compared to healthy peers.

## Contribution

The study identifies specific cytokine profiles and inflammatory imbalances in drug-naïve adolescent anorexia nervosa patients.

## Key findings

- Adolescent AN girls showed significantly higher plasma levels of IL-1β, IL-6, and TNF-α compared to controls.
- BMI and depressive symptoms were linked to altered cytokine levels in AN patients.
- A combination of cytokine markers achieved high accuracy in distinguishing AN from controls.

## Abstract

Anorexia nervosa (AN) represents a relatively common eating disorder associated with the highest mortality from all mental disorders. However, the underlying AN psychobiology remains unclear. The disruption in immune pathways seems to play an important pathophysiological role in AN. Therefore, this study aimed to evaluate the cytokine profile in association with assessing the pro-inflammatory/anti-inflammatory balance in drug-naïve adolescent AN girls in the early stage of the disease.

Selected cytokines including interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma, tumor necrosis factor-alpha (TNF-α) were evaluated in 35 adolescent AN girls (mean age: 15.0 ± 1.6 years) and 25 age-matched control adolescent girls (mean age: 15.9 ± 1.5 years). Moreover, selected cytokine profiles and cytokine ratios were calculated to evaluate the pro-inflammatory/anti-inflammatory balance in adolescent AN. The presence and severity of depressive symptomatology were evaluated by full-filling the standardized and validated Children´s Depression Inventory.

The plasma levels of IL-1β, IL-6, TNF-α, M1 profile, pro-inflammatory profile, Th1/Th2 ratio, Th1/Treg ratio, Th1/Th2 + Treg ratio, and pro-inflammatory/anti-inflammatory ratio were significantly higher in AN adolescent girls compared to controls (p = 0.002, p = 0.009, p = 0.031, p < 0.001, p = 0.042, p = 0.031, p = 0.021, p = 0.016, p = 0.001; respectively). On the other hand, the plasma level of IL-1α was significantly lower in AN adolescent girls compared to controls (p = 0.005). Moreover, BMI predicted levels of IL-4 and IL-1β (p = 0.009, p = 0.046, respectively), and depressive symptomatology predicted level of IL-8 (p = 0.012) in adolescent AN girls. Lastly, ROC analysis revealed a certain predictive value of significantly changed cytokines, cytokine profiles, and ratios in adolescent AN, which markedly improved by the combination of these parameters (AUC = 0.930). Moreover, cross-validation analysis of the combined model AUC using the K-Nearest Neighbors model achieved a high overall accuracy of 0.917 for both groups, with a precision of 1.000 for the AN and 0.800 for the controls.

Adolescent drug-naïve AN in early stages of the disease is characterized by enhanced IL-1β, IL-6, and TNF-α signalling indicating the activation of pro-inflammatory response system. Whether these inflammatory abnormalities are AN-specific or related to other confounding aspects of the disease still needs to be resolved, since BMI and depressive symptomatology contributed to the alterations in evaluated inflammatory markers in this study.

Not applicable.