interleukin-8 and Anxiety-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

We have shown that treatment with interleukin-2 (IL-2) or interferon-alpha (IFN alpha) may induce depressive symptoms and activation of the cytokine network and that IL-2 treatment may diminish serum dipeptidyl pepdidase IV (DPP IV) activity. DPP IV (EC 3.4.14.5) is a membrane bound serine protease which catalyzes the cleavage of some cytokines and neuroactive peptides which modulate T cell activity. The aims of the present study were to examine the effects of IFN alpha-based immunotherapy on serum DPP IV activity in relation to induction of the inflammatory response system. In 18 patients with chronic active hepatitis C, we determined the Montgomery and Asberg Rating Scale (MADRS), the Hamilton Anxiety Rating Scale (HAM-A), serum DPP IV activity, the kynurenine/tryptophan (K/T) quotient, which is an indicator of cytokine (in particular IFN)-induced catabolism of tryptophan, and serum interleukin-8 (IL-8) before starting therapy and 2, 4, 16 and 24 weeks after immunotherapy with IFN alpha. IFN alpha-immunotherapy significantly suppressed serum DPP IV 2--4 weeks and 16--24 weeks after starting IFN alpha-based immunotherapy. The reduction in serum DPP IV activity was more pronounced 16--24 weeks after starting immunotherapy than after 2--4 weeks. The IFN alpha-induced suppression of serum DPP IV activity was significantly correlated to IFN alpha-induced increases in the MADRS and HAM-A and increases in the K/T quotient and serum IL-8. In conclusion, long-term immunotherapy with IFN alpha suppresses serum DPP IV activity and the immunotherapy-induced changes in DPP IV are related to increases in severity of depression, anxiety and activation of the inflammatory response system.

Topics: Adult; Analysis of Variance; Antiviral Agents; Anxiety Disorders; Biomarkers; Depression; Dipeptidyl Peptidase 4; Dose-Response Relationship, Drug; Female; Hepatitis C, Chronic; Humans; Inflammation; Interferon alpha-2; Interferon-alpha; Interleukin-8; Male; Psychiatric Status Rating Scales; Recombinant Proteins; Regression Analysis; Time Factors

Childhood trauma (CT) is robustly associated with psychiatric disorders including major depressive and anxiety disorders across the life span. The innate immune system may play a role in the relation between CT and stress-related psychopathology. However, whether CT influences the innate production capacity of cytokine levels following ex vivo stimulation by lipopolysaccharide (LPS), is currently unknown.. Using data from the Netherlands Study of Depression and Anxiety (NESDA, n=1237), we examined whether CT (emotional neglect, emotional, physical, and sexual abuse before the age of 16), assessed by the Childhood Trauma Interview, was associated with levels in supernatants of interferon (IFN)γ, interleukin-2 (IL-2), IL-4, IL-6, IL-8, IL-10, IL-18, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1α, MIP-1β, matrix metalloproteinase-2 (MMP-2), TNFα and TNFβ after ex vivo stimulation with LPS. Cytokines were analysed individually and cumulatively (overall inflammation index and number of cytokines in high-risk quartile (HRQ)) using linear regression analyses.. After adjustment for demographic, lifestyle, and health-related covariates, total CT severity was associated with the overall inflammation index (β = 0.085, P. Childhood Trauma is associated with increased LPS-stimulated cytokine levels, with evidence for a dose-response relationship. Our results highlight a dysregulated innate immune system capacity in adults with CT, which could contribute to an increased vulnerability for psychopathology and somatic disorders across the lifespan.

Topics: Adult; Adverse Childhood Experiences; Anxiety; Anxiety Disorders; Chemokine CCL2; Chemokine CCL3; Chemokine CCL4; Cytokines; Depression; Depressive Disorder, Major; Humans; Immunity, Innate; Inflammation; Interferons; Interleukin-10; Interleukin-18; Interleukin-2; Interleukin-4; Interleukin-6; Interleukin-8; Lipopolysaccharides; Matrix Metalloproteinase 2; Netherlands; Tumor Necrosis Factor-alpha

Substance use disorders (SUD) with comorbid depression and anxiety are linked to poor treatment outcome and relapse. Although some depressed individuals exhibit elevated blood-based inflammation (interleukin-6 [IL-6] and C reactive protein [CRP]), few studies have examined whether the presence of SUD exacerbates inflammation.. Treatment-seeking individuals with major depressive disorder (MDD), anxiety disorders, and/or SUD (N = 160; 80 % with MDD) recruited into the Tulsa 1000 study provided blood samples, participated in clinical interviews, and completed a questionnaire battery querying symptoms of current psychopathology and emotional processing. Analyses followed a multistep process. First, groups were created on the presence versus absence of 1+ lifetime SUD diagnoses: SUD+ (37 F, 43 M) and SUD- (60 F, 20 M). Second, a principal component analysis (PCA) of questionnaire data resulted in two factors, one indexing negative emotionality/withdrawal motivation and one measuring positive emotionality/approach motivation. Third, SUD groups, extracted PCA factors, and nuisance covariates (age, body mass index [BMI], nicotine use, psychotropic medication [and hormone/contraception use in females]) were entered as simultaneous predictors of blood-based inflammation (IL-6, IL-8, IL-10, tumor necrosis factor-α, and CRP).. Within females, SUD + exhibited higher IL-8 and IL-10 but lower CRP levels than SUD-. In contrast, SUD was not associated with biomarker levels in males. Across sexes, higher BMI was linked to higher IL-6 and CRP levels, and within the five biomarkers, IL-6 and CRP shared the most variance.. These findings point to sex-specific inflammatory profiles as a function of SUD that may provide new targets for intervention.

Topics: Adult; Anxiety Disorders; Biomarkers; Body Mass Index; C-Reactive Protein; Depressive Disorder, Major; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Psychopathology; Sex Factors; Substance-Related Disorders; Tumor Necrosis Factor-alpha

In cross-sectional studies of depressed patients, relationships between depression and levels of IL-8 are inconsistent, and have not been examined in relation to sex. Given identified sex differences in longitudinal data, it is important to evaluate sex-specific cross-sectional relationships between IL-8 and depressive symptoms, which may explain some inconsistency in the extant literature. It is further unknown whether IL-8 levels may relate to specific symptom profiles among depressed patients, with or without regard to sex.. Among 108 patients with treatment resistant depression (50 females), we evaluated cross-sectional relationships between IL-8 and depression severity, as measured by the Hamilton Depression Rating Scale [HAM-D] Score, and examined sex-specific relationships, as well as relationships with depressive symptom profiles. Other inflammatory markers (IL-6, IL-10, TNF-α, CRP) were also explored in relation to HAM-D.. IL-8 may be related to anxiety symptoms across sexes, but may have a sex-specific relationship with other depressive symptoms. Further evaluation of sex-specific relationships between IL-8, depression symptom profiles, treatment response, and potential neurobiological correlates, may inform mechanisms of depression pathophysiology and aid in development of precision medicine strategies.

Topics: Anxiety Disorders; Cross-Sectional Studies; Depression; Depressive Disorder, Treatment-Resistant; Female; Humans; Interleukin-8; Male

Inflammatory responses and inflammatory cytokines have been implicated in the pathogenesis of affective disorders, particularly major depression. Given the limited evidence relating to the potential role of proinflammatory cytokines in generalised anxiety disorder (GAD), we aimed to examine peripheral proinflammatory cytokines in Chinese patients with GAD.. A case-controlled cross-sectional study design, with recruitment of 48 patients with first episode GAD and 48 matched healthy controls. All participants completed measures of anxiety using well-established questionnaires, and serum levels of pro-inflammatory cytokines were measured using multiplex technology.. Serum levels of CRP, IL-1α, IL-2, IL-6, IL-8, IL-12, IFN-γ, and GM-CSF were significantly higher in the GAD group in comparison to the control group (p < 0.05). Pearson correlation revealed significant positive correlations between anxiety measures and serum levels of CRP, IL-1α, IL-6, IL-8, IFN-γ, and GM-CSF (p < 0.05).. The cross-sectional study design does not permit definite conclusions on causal directions between inflammation and GAD. The study was limited to a panel of 8 cytokines and does not exclude the possibility of other important cytokines being involved.. These findings indicate an elevated peripheral proinflammatory response, and provide further support for low grade inflammation in GAD. Further research may identify an 'inflammatory signature' for diagnosis and treatment response, and guide the search for novel pharmacological interventions.

Topics: Adult; Anxiety Disorders; Asian People; Case-Control Studies; Cross-Sectional Studies; Cytokines; Female; Humans; Inflammation Mediators; Interleukin-12; Interleukin-1alpha; Interleukin-2; Interleukin-6; Interleukin-8; Male; Middle Aged

It is evident that immune cytokines are involved in the pathophysiology of posttraumatic stress disorder (PTSD), but results of different studies are still inconsistent. Here, serum interleukin (IL)-2, IL-6 and IL-8 levels were compared between earthquake survivors with PTSD, those with non-PTSD and normal controls to investigate whether there is any relationship between cytokine levels and PTSD. In addition, the relationship of these cytokines with psychological parameters of the disorder was examined as well.. Thirty-four earthquake survivors with PTSD (according to DSM-IV criteria), 30 earthquake survivors with non-PTSD and 34 controls were recruited in northern China using the Composite International Diagnostic Interview instrument. Serum IL-2, IL-6 and IL-8 levels were compared. IL-2 levels were measured by radioimmunometric assay, while serum IL-6 and IL-8 levels were measured using sandwich enzyme-linked immunosorbent assay. Psychological symptoms were assessed using 3 subscales of the Symptoms Checklist (SCL-90-R), including depression, anxiety and somatization.. Only earthquake survivors diagnosed with PTSD had significantly lower serum IL-8 levels. Also, we found that earthquake survivors (either with PTSD or non-PTSD) had significantly lower serum IL-2 levels and more severe psychological symptoms. The severity of depressive and anxiety symptoms in earthquake survivors was positively related to serum IL-6 levels.. PTSD may be associated with a reduced level of serum IL-8, and traumatic survivors may be associated with a lower level of serum IL-2.

Topics: Anxiety Disorders; Biomarkers; China; Depressive Disorder; Disasters; Immune System Diseases; Interleukin-2; Interleukin-6; Interleukin-8; Interleukins; Radioimmunoassay; Stress Disorders, Post-Traumatic; Stress, Psychological