IL-8 and the innate immunity as biomarkers in acute child and adolescent psychopathology

Abstract

Objective: The role of inflammation in psychopathology has received great attention over the past decades. Immune system dysfunction and altered cytokine levels have been reported in most psychiatric disorders in adults. Few data are available regarding children and adolescents (C&A), or regarding the relationship between cytokine levels and psychosocial stress. This study investigates the profile of the most described cytokines in a sample of C&A inpatients affected by an acute psychiatric condition requiring hospitalization, in comparison with healthy subjects, as well as possible associations between psychosocial stressors and psychopathology and/or cytokine concentrations.

Methods: Patients with a diagnosis of Affective, Anxiety, Adjustment, Psychotic, Obsessive-Compulsive, Tic or Tourette Disorders were consecutively recruited from our clinic between June 2010 and February 2012. Controls were recruited from the same geographic area. All subjects were between 8 and 17 years old. Twelve cytokines are compared: interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL_10, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IFN-γ-induced protein-10 (IP-10), monocyte chemoattractant protein (MCP)-1. Psychosocial stress was measured through the Stressful Life Events Scale, Child and Parents versions (SLES-C and SLES-P) and the evaluation of the family integrity.

Results: One hundred and eleven subjects (77C&A inpatients and 34 healthy controls), of which 54 were males (49%), with a median (interquartile range) age of 16 (13.7-17.3) years, were included in this study. IL-1β, IL6, IL8, IP-10, MCP-1 and monocytes were found to be significantly higher in the patient group (p<0.05). Differences were confirmed when adjusting by BMI, age, gender and drug intake at admission for all cytokines except MCP-1. IL-8 and IL-1β were also higher throughout the different diagnostic categories, than in control group (p<0.05). Stress measures were higher in patients. A significant correlation was found between stress measured by the SLES and some inflammatory markers: SLES_C with IL-1β, IL-8, MCP-1, and SLES_P with IL-1β and monocytes absolute and relative counts (Spearman's r between 0.219 and 0.297, p<0.05). Logistic regression identified the following variables as independent predictors of the patient condition, (odds ratio per quartile, p-value): IL8 (1, 0.9, 12.1, 32.0, p=0.044), IP10 (1, 14.1, 2.5, 3.7, p=0.044), monocyte absolute count (1, 1.1, 6.0, 19.4, p=0.030).

Conclusions: Results show elevated inflammation markers from the innate immune system across C&A acute psychiatric diagnosis, and suggest a link between psychopathology, inflammation and stress. Inflammatory markers resulted predictors of patient status. These exploratory results are coherent with current psychoneuroimmunology and neurodevelopmental investigations.

Keywords: Child and adolescent psychiatry; Cytokines; IL-8; Inflammation; Psychoneuroimmunology; Stress.