The Kynurenine Pathway is Differentially Activated in Children with Lyme Disease and Tick-Borne Encephalitis.

Ronny Wickström,Vincent Millischer,Åsa Fowler,Sofia Ygberg,Michel Goiny,Lilly Schwieler

doi:10.3390/microorganisms9020322

Ronny Wickström, Vincent Millischer + Show 4 more

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https://doi.org/10.3390/microorganisms9020322

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Abstract

In children, tick-borne encephalitis and neuroborreliosis are common infections affecting the central nervous system. As inflammatory pathways including cytokine expression are activated in these children and appear to be of importance for outcome, we hypothesized that induction of the kynurenine pathway may be part of the pathophysiological mechanism. Inflammatory biomarkers were analyzed in cerebrospinal fluid from 22 children with tick-borne encephalitis (TBE), 34 children with neuroborreliosis (NB) and 6 children with no central nervous system infection. Cerebrospinal fluid levels of kynurenine and kynurenic acid were increased in children with neuroborreliosis compared to the comparison group. A correlation was seen between expression of several cerebrospinal fluid cytokines and levels of kynurenine and kynurenic acid in children with neuroborreliosis but not in children with tick-borne encephalitis. These findings demonstrate a strong induction of the kynurenine pathway in children with neuroborreliosis which differs from that seen in children with tick-borne encephalitis. The importance of brain kynurenic acid (KYNA) in both immune modulation and neurotransmission raises the possibility that abnormal levels of the compound in neuroborreliosis might be of importance for the pathophysiology of the disease. Drugs targeting the enzymes of this pathway may open the venue for novel therapeutic interventions.

Highlights

In children, tick-borne encephalitis (TBE) and neuroborreliosis (NB) are among the most common infections affecting the central nervous system (CNS) [1,2]
cerebrospibrospinal fluid (CSF) concentrations of kynurenine or kynurenic acid (KYNA) were not statistically significant different between children with TBE and children included in the comparison group
We found that seven cytokines correlated to kynurenine and five to KYNA in CSF from children with NB, but no correlations were found with any of the tryptophan metabolites in CSF

Summary

Introduction

Tick-borne encephalitis (TBE) and neuroborreliosis (NB) are among the most common infections affecting the central nervous system (CNS) [1,2]. The reported incidence for TBE in Swedish children is around 3/100,000 [3], whereas the incidence for NB is substantially higher at 28/100,000 [4]. The clinical picture in children differs from that seen in adults and is often vague with unspecific symptoms which may delay diagnosis [5]. The pathophysiological mechanisms underlying the differences seen in outcome (varying from mild to severe) are not known, but several studies suggest that either systemic or local production of various cytokines might play a pathophysiologic role [6,7,8]. A recent study from our group confirms a strong immune activation in both children with

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