Changes of Cytokines in Children With Tic Disorder

Abstract

Tic disorder (TD) is a common childhood-onset disease associated with abnormal development of brain networks involved in the motor and sensory processing. The underlying pathophysiological mechanisms in TD are still unclear. An involvement of immune mechanisms in its pathophysiology has been proposed. This study investigates the association between the changes of cytokines and the etiology and development of TD. Different expressions of cytokines in a larger number of samples in our study may provide new insights to the field. The levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were evaluated in 1,724 patients who were clinically diagnosed with TD from 1 to 17.5 years old and 550 were from 6 months to 14.5 years old in the control group. We assessed the levels of cytokines according to the patient's medication status and the severity of the disease. Of the cytokines we investigated, the serum IL-6 concentration of children with TD was significantly higher than that of the control group, while the levels of other cytokines were lower in TD patients. In the patient group whose YTGSS score ranged from 1 to 9, the IL-4, IL-10, and IFN-γ levels increased in medication group compared to unmedication group. Our data suggested that the cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) may play an important role in the etiology and the severity in TD. Whether drug intervention in the early stage of tic disorder has a better effect on children needs further research.

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“…Interleukin-6 ( IL-6 ) has both proinflammatory and anti-inflammatory activities ( 28 , 29 ) and contributes to the transition from acute inflammation to chronic inflammation ( 30 ). IL-6 is a multidirectional cytokine that has important roles in both the immune system and the nervous system, affecting mood, sleep, and neuroimmune regulation, among others.…”

Cytokine Levels Reflect Tic Symptoms more Prominently During Mild Phases

“…compared tic disorder patients with controls, determining that patients had higher levels of IL-6 while levels of IL-2, IL-4, IL10, TNF-α, and IFN-γ were lower than controls [17]. Leckman et al also compared tic disorder patients and healthy controls, showing that the patients had elevated IL-12 and TNF-α levels [25].…”

Cytokine levels reflect tic symptoms more prominently during mild phases

“…Previous studies have investigated the relationship between tic disorders and cytokines to identify the cytokines that play key roles. A recent research by Tao et al compared tic disorder patients with controls, determining that patients had higher levels of IL-6 while levels of IL-2, IL-4, IL10, TNF-α, and IFN-γ were lower than controls [ 18 ]. Leckman et al also compared tic disorder patients and healthy controls, showing that the patients had elevated IL-12 and TNF-α levels [ 30 ].…”

“…Parker-Athill showed that TNF-α levels were associated with tic symptom exacerbation [ 17 ]. A Chinese study on 1724 tic disorder patients also showed that TNF-α among other cytokines increased in levels as symptoms get more severe, although statistical significance was not reached [ 18 ].…”

“…Another recent study also divided tic disorder patients into minimal, mild, and moderate-to-severe symptom groups, where only the mild symptom group showed increased TNF-α levels [ 33 ]. Tao et al also pointed out that patients with mild symptoms (YGTSS scores below 10) IL-4, IL-10, and IFN-γ levels were significantly lower in medicated patients than in unmedicated patients whereas moderate and severe symptomatic patients did not show differences [ 18 ].…”