Dopamine up-regulates Th17 phenotype from individuals with generalized anxiety disorder.
ABSTRACT Our objective was to evaluate the effect of stress-related dose of dopamine (DA) on the in vitro proliferation and cytokine production in polyclonally-activated T cells from healthy individuals or individuals with generalized anxiety disorder (GAD). Our results demonstrated that cell cultures from GAD group proliferated less following T cell activation, as compared with control group. The addition of DA reduced the proliferative response in cell cultures from healthy but not from GAD individuals. The cytokine profile in GAD individuals revealed Th1 and Th2 deficiencies associated with a dominant Th17 phenotype, which was enhanced by DA. A similar DA-induced immunomodulation was also observed in PPD-activated cell cultures from GAD individuals. Unlike the control, DA-enhanced Th17 cytokine production in GAD individuals was not affected by glucocorticoid. In conclusion, our results show that the T cell functional dysregulation in GAD individuals is significantly amplified by DA. These immune abnormalities can have impact in increasing the susceptibility of individuals with anxiety disorders to infectious diseases and inflammatory/autoimmune disorders.
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ABSTRACT: There is some evidence that schizophrenia may be accompanied by alterations in cell-mediated immunity (CMI) and that antipsychotic agents may modulate CMI. The purpose of this study was to investigate the plasma levels of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), sIL-2R, and transferrin-receptor (TfR) in schizophrenia and mania, and the effects of treatment with neuroleptics or mood stabilizers on these variables. The subjects were 14 schizophrenic patients, 10 manic patients and 21 healthy volunteers. The above immune variables were measured in baseline conditions and after treatment with neuroleptics in schizophrenic patients and valproate in manic patients. Plasma concentrations of IL-6, sIL-6R, sIL-2R and TfR were significantly higher in the combined group of psychotic patients than in healthy volunteers. Plasma IL-6 was significantly higher in schizophrenic patients, while plasma sIL-6R and sIL-2R were significantly higher in mania than in normal controls. In schizophrenic patients, plasma levels of IL-6, sIL-6R and TfR were significantly lower after treatment with neuroleptics than before treatment. No significant effects of valproate on the immune-inflammatory markers could be found in the manic patients. It is suggested that activation of CMI may occur in both schizophrenia and mania and that neuroleptics may have immunosuppressive effects through suppression of IL-6 or IL-6R-related mechanisms.Journal of Psychiatric Research 01/1995; 29(2):141-52. · 4.07 Impact Factor
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ABSTRACT: The following study tested the hypothesis that women with post-traumatic stress disorder (PTSD) related to childhood sexual abuse would display elevated norepinephrine-to-cortisol ratios similar to that found in male combat veterans diagnosed with PTSD. Twenty-four-hour urine samples were collected from 28 women: 11 women with PTSD who experienced childhood sexual abuse (PTSD+), 8 women who experienced childhood sexual abuse without PTSD (PTSD-), and 9 nonabused controls. All urine samples were tested for creatinine, total catecholamines, free-cortisol, and 17-ketosteroid levels. Psychological testing validated that the PTSD+ group was significantly elevated on all three subscales of the Impact of Events Scale. Both abused groups (PTSD+ and PTSD-) showed a tendency for polyuria, and the PTSD+ group showed a tendency towards obesity. Thus, neuroendocrine values (micrograms/day) were adjusted by creatinine clearance rates (creatinine mg/day/kg body weight). The corrected values indicated that the PTSD+ group had significantly elevated daily levels of norepinephrine, epinephrine, dopamine, and cortisol. However, because of the parallel elevation in cortisol, the norepinephrine-to-cortisol ratio was not significantly elevated in the PTSD+ diagnosed women in contrast to the findings reported for male PTSD patients. This discrepancy may reflect an important gender difference, an interaction between gender and age at onset of the traumatic experience (childhood abuse in females vs. combat experience in young adult males), or physiological variation related to phase of the disorder.Psychosomatic Medicine 57(2):105-15. · 4.08 Impact Factor
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ABSTRACT: Table I summarizes the properties of all of the dopamine receptors that have been cloned to date. Thus far, five different genes encoding pharmacologically distinct receptors have been identified and isolated. Based on their structural, pharmacological, and functional similarities, two of these, D1A and D1B (or D1 and D5), comprise the D1 subfamily. D2, D3, and D4 receptors represent a D2 subfamily whose members are also structurally and pharmacologically similar. In fact, given these considerations, it has been suggested that the D2, D3, and D4 receptors be termed the D2A, D2B, and D2C receptors, respectively, in recognition of their D2-like properties. Given the unexpected heterogeneity of the dopaminergic receptor system, it is logical to ask if there are other dopamine receptor subtypes remaining be identified. This seems probable, as the characteristics of the cloned subtypes do not match all of the properties of some dopamine receptors which have been previously investigated. For instance, there is extensive evidence that "D1-like" dopamine receptors exist which are linked to the activation of phospholipase C, phosphatidylinositol turnover, and Ca2+ mobilization. Dopamine, as well as several "D1-selective" agonists, has been shown to stimulate phosphatidylinositol turnover in both brain slices and kidney membranes (Felder et al., 1989; Undie and Friedman, 1990; Vyas et al., 1992), and injection of striatal mRNA into Xenopus oocytes leads to dopamine-stimulated phosphatidylinositol turnover and Ca2+ mobilization (Mahan et al., 1990). These dopamine receptors might be analogous to the alpha 1-adrenergic receptors which stimulate phospholipase C activity and might define a third distinct subfamily of dopamine receptors. There is also evidence for additional members of the D2 subfamily of receptors. Using gene transfer methods, a receptor with D2-like pharmacology has been identified and expressed but not yet sequenced (Todd et al., 1989). Also, a D2-related receptor has been characterized in kidney inner medulla membranes (Huo et al., 1991). It thus appears that there may be more dopamine receptor subtypes yet to be discovered.International Review of Neurobiology 02/1993; 35:391-415. · 1.65 Impact Factor