interleukin-8 and Mental-Disorders

Low grade neuroinflammation has been suggested as one of the underlying mechanisms of many psychiatric diseases as well as cognitive disorders. Interleukin 8 (IL-8), a proinflammatory cytokine produced by many cell types including macrophage and microglia, mainly functions as a neutrophil chemoattractant in the bloodstream. IL-8 is also found in the brain, where it is released from microglia in response to proinflammatory stimuli. In this review, we highlight studies focusing on the role of IL-8 in psychiatric diseases such as major depression, bipolar disorder, schizophrenia, sleep disorder, autism spectrum disorder, anxiety disorders and dementia. Increased peripheral IL-8 levels have been reported in these diseases, particularly in schizophrenic disorder, bipolar disorder, obstructive sleep apnea and autism spectrum disorder. The literature on IL-8 and major depression is inconsistent. IL-8 has been found to be a factor associated with schizophrenic prognosis and therapeutic response, and may affect a wide range of symptomatology. Considering that the exact role of immune alterations is still under research, the success of immune-based therapies in psychiatric diseases is limited for the time being.

Topics: Animals; Anxiety Disorders; Depression; Humans; Immunotherapy; Inflammation Mediators; Interleukin-8; Mental Disorders; Neuroinflammatory Diseases; Schizophrenia; Sleep Wake Disorders

Major psychiatric disorders are associated with inflammation. Aberrant cytokine and chemokine levels have been associated with psychiatric disorders and suicidal behavior. We performed a meta-analysis of cytokine and chemokine levels in patients with versus without suicidality and patients with suicidality versus healthy controls.. We identified articles by searching MEDLINE, PsycINFO, and Thomson Reuters Web of Knowledge databases and the reference lists of identified studies.. Study inclusion criteria were met by 18 studies comprising 583 patients with suicidality, 315 patients without suicidality, and 845 healthy control subjects. Levels of interleukin (IL)-1β and IL-6 were significantly increased in blood and postmortem brain samples of patients with suicidality compared with both patients without suicidality and healthy control subjects (p < .05 for each). In vitro IL-2 production by peripheral blood mononuclear cells was significantly decreased in patients with suicidality compared with both patients without suicidality and healthy controls (p < .01 for each). Cerebrospinal fluid levels of IL-8 were significantly decreased in patients with suicidality versus control subjects (p < .05).. We found evidence for aberrant cytokine levels in blood, cerebrospinal fluid, and postmortem brain samples of patients with suicidality. Levels of IL-1β and IL-6 were most robustly associated with suicidality, and these cytokines may help distinguish suicidal from nonsuicidal patients. Rigorously designed longitudinal studies are needed to evaluate these associations further.

Topics: Adolescent; Adult; Brain; Chemokines; Cytokines; Female; Humans; Inflammation; Interleukin-1beta; Interleukin-8; Male; Mental Disorders; Middle Aged; Receptors, Interleukin-6; Suicide

Psychological stress has repeatedly been found to be associated with pro-inflammatory markers in blood, and neuro-inflammation may play a role in the development of psychopathology after early life stress. Salivary immune testing is a novel method to non-invasively assess immune functioning. We examined a large range of salivary immune markers in relation to self-reported childhood maltreatment and psychopathology in an adult sample.. Participants (N = 118, 51% female, mean age = 46.6 yrs, range 22-64) were drawn from a cross-sectional three-generation study, and supplied 2 ml of saliva via passive drool. They reported on childhood maltreatment experiences and on psychopathological symptoms in the last 6 months. Hair cortisol was additionally assessed in a subsample (n = 68). Levels of IL1ß, IL6, IL8, IFNγ, TNFα, tIgE, sIgA, FLCƛ, and FLCƙ were assessed.. Linear mixed model analyses showed that several salivary immune markers were associated with age (sIgA and IgE), BMI (sIgA, IL1ß, and IL6), sex (FLCs and IgE), and bad health (IL6, IL8, TNFα). No associations with (anti-inflammatory) medication use or oral health problems were found. Notably, no associations between the immune markers and self-reported childhood maltreatment, psychopathology, or hair cortisol were found.. Salivary immune measures were found to be sensitive to individual differences in age, sex, health and BMI. However. in the current sample there was no indication of inflammation in relation to chronic psychological stress. Larger studies, including participants with higher stress levels, are needed to further examine associations between salivary immune markers and psychological stress.

Topics: Adult; Biomarkers; Child; Child Abuse; Cross-Sectional Studies; Female; Humans; Hydrocortisone; Immunoglobulin A, Secretory; Immunoglobulin E; Inflammation; Interleukin-6; Interleukin-8; Male; Mental Disorders; Middle Aged; Psychopathology; Saliva; Self Report; Stress, Psychological; Tumor Necrosis Factor-alpha; Young Adult

Research suggests that maternal immune activation (MIA) during pregnancy increases the risk of neurodevelopmental disorders including schizophrenia and autism in the offspring. Current theories suggest that inflammatory mediators including cytokines and chemokines may underlie the increased risk of these disorders in humans. For example, elevated maternal interleukin-8 (IL-8) during pregnancy is associated with increased risk of schizophrenia in the offspring. Given this association, the present experiments examined ELR-CXC chemokines CXCL1 and CXCL2, rodent homologues of human IL-8, and activation of their receptors (CXCR1 and CXCR2) in an established rodent model of MIA. Pregnant Long Evans rats were treated with the viral mimetic polyinosinic-polycytidylic acid (polyI:C; 4 mg/kg, i.v.) on gestational day 15. Protein analysis using multiplex assays and ELISA showed that polyI:C significantly increased maternal serum concentrations of interleukin-1β, tumor necrosis factor, and CXCL1 3h after administration. Subsequent experiments tested the role of elevated maternal CXCL1 on behavior of the offspring by administering a CXCR1/CXCR2 antagonist (G31P; 500 μg/kg, i.p.; 1h before, 48 and 96 h after polyI:C treatment). The male offspring of dams treated with polyI:C demonstrated subtle impairments in prepulse inhibition (PPI), impaired associative and crossmodal recognition memory, and altered behavioral flexibility in an operant test battery. While G31P did not completely reverse the behavioral impairments caused by polyI:C, it enhanced PPI during adolescence and strategy set-shifting and reversal learning during young adulthood. These results suggest that while polyI:C treatment significantly increases maternal CXCL1, elevations of this chemokine are not solely responsible for the effects of polyI:C on the behavior of the offspring.

Topics: Animals; Behavior, Animal; Chemokine CXCL1; Chemokine CXCL2; Conditioning, Operant; Cues; Female; Interleukin-8; Male; Mental Disorders; Peptide Fragments; Poly I-C; Pregnancy; Pregnancy, Animal; Prenatal Exposure Delayed Effects; Prepulse Inhibition; Rats; Rats, Long-Evans; Receptors, CXCR; Receptors, Interleukin-8A; Receptors, Interleukin-8B; Recognition, Psychology; Schizophrenia

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.. 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.. 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).. 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.

Topics: Adolescent; Biomarkers; Child; Cytokines; Female; Humans; Immunity, Innate; Inflammation; Interleukin-8; Male; Mental Disorders