Fractalkine, sICAM-1 and Kynurenine Pathway in Restrictive Anorexia Nervosa-Exploratory Study.

Ewa Dudzińska,Janusz Kocki,Jacek Bogucki,Roman Paduch,Ewa M Urbańska,Paulina Gil-Kulik,Renata Kloc,Tomasz Kocki,Kinga Szymona

doi:10.3390/nu13020339

Ewa Dudzińska, Janusz Kocki + Show 7 more

Open Access

https://doi.org/10.3390/nu13020339

Copy DOI

Abstract

The link between the kynurenine pathway and immunomodulatory molecules—fractalkine and soluble intercellular adhesion molecule-1 (sICAM-1)—in anorexia nervosa (AN) remains unknown. Fractalkine, sICAM-1, tryptophan (TRP), kynurenine (KYN), neuroprotective kynurenic acid (KYNA), neurotoxic 3-OH-kynurenine (3-OH-KYN), and the expression of mRNA for kynurenine aminotransferases (KAT1-3) were studied in 20 female patients with restrictive AN (mostly drug-free, all during first episode of the disease) and in 24 controls. In AN, serum fractalkine, but not sICAM-1, KYNA, KYN, TRP or 3-OH-KYN, was higher; ratios TRP/KYN, KYN/KYNA, KYN/3-OH-KYN and KYNA/3-OH-KYN were unaltered. The expression of the gene encoding KAT3, but not of genes encoding KAT1 and KAT2 (measured in blood mononuclear cells), was higher in patients with AN. In AN, fractalkine positively correlated with TRP, while sICAM-1 was negatively associated with 3-OH-KYN and positively linked with the ratio KYN/3-OH-KYN. Furthermore, TRP and fractalkine were negatively associated with the body mass index (BMI) in AN. Expression of KAT1, KAT2 and KAT3 did not correlate with fractalkine, sICAM-1 or BMI, either in AN or control. Increased fractalkine may be an independent factor associated with the restrictive type of AN. Excessive physical activity probably underlies increased expression of KAT3 observed among enrolled patients. Further, longitudinal studies on a larger cohort of patients should be aimed to clarify the contribution of fractalkine and KAT3 to the pathogenesis of AN.

Highlights

IntroductionAlterations of the hypothalamic–pituitary–adrenal (HPA) axis, changes in the neurotransmitter systems and immune dysfunction have all been linked to the disturbed regulation of food intake in anorexia nervosa (AN) [4,5,6]
The ratios TRP/KYN, KYN/kynurenic acid (KYNA), KYN/3-OH-KYN and KYNA/3-OH-KYN in anorexia nervosa (AN) group were not changed vs. control (Table 2)
Increased level of fractalkine may, constitute an independent factor associated with restrictive type of AN

Summary

Introduction

Alterations of the hypothalamic–pituitary–adrenal (HPA) axis, changes in the neurotransmitter systems and immune dysfunction have all been linked to the disturbed regulation of food intake in AN [4,5,6]. The contribution of altered immune response to the pathogenesis of AN is an attractive hypothesis; the available data are rare and the results are often contradictory [7,8]. The dysregulation of the cytokine profile in AN is supported by the observations of an altered proportion between pro- and anti-inflammatory cytokines in the blood of patients. Some, but not all, of the pro-inflammatory molecules seem to be down-regulated during an acute phase of the disease [8,9,10]. Lower levels of nineteen and higher levels of six inflammation-related molecules, including various cytokines, were detected in acute AN, but not during recovery period [11]

Methods

Results

Discussion

Conclusion