Neuroleptic treatment increases soluble IL-2 receptors and decreases soluble IL-6 receptors in schizophrenia

The cytokines interleukin-2 (IL-2) and interleukin-6 (IL-6) increase during immune activation, they are released from activated astrocytes and microglial cells in the central nervous system (CNS), and they are able to enhance the catecholaminergic neurotransmission. This study focused on the soluble receptors of IL-2 and IL-6 (sIL-2R, sIL-6R) as a part of the regulation system of IL-2 and IL-6. We studied serum levels of sIL-2R in 30 schizophrenic patients not under neuroleptic medication during an acute exacerbation of the disease and reexamined these patients under neuroleptic treatment after clinical improvement. The SIL-6R levels of 39 schizophrenic patients were estimated under the same conditions. The results were compared with the levels of sIL-2R and sIL-6R in 42 healthy controls. No difference was found between the schizophrenic patients before neuroleptic treatment and the healthy controls. During neuroleptic treatment, however, there was a significant increase of sIL-2R levels and a significant decrease of the sIL-6R levels between the pre- and post-conditions. In comparison with healthy controls, the treatment group also showed increased sIL-2R levels and decreased sIL-6R levels. These results suggest that treatment with neuroleptics is associated with increased sIL-2R and decreased sIL-6R. Since sIL-2R bind and inactivate IL-2, whereas sIL-6R form an active complex with IL-6, the increase of sIL-2R and the decrease of sIL-6R together may reflect a functional down regulation of these activating cytokines. This suggests that neuroleptic therapy has a differentiated immunomodulatory effect.     

Diurnal variations of EEG power in healthy adults

EEG power variations were evaluated in 9 healthy young adults from 8.45 a.m. to 9 p.m. and at 7 a.m. the next day. EEG signals were obtained from 16 electrodes in closed eyes and open eyes situations. Diurnal power variations were calculated for each frequency component, according to the recording situation (RS) and to the scalp site. Regarding values in the early morning on the first day, the power of almost all the frequency components showed an important diurnal increase. It came back close to initial values at 7 a.m. on the second day, which is in agreement with the existence of EEG circadian variations. Diurnal evolutions were dependent on the frequency components: the higher the frequency, the later was its diumal maximum. For many frequency components, the diurnal variation was dependent on RS and the scalp topography. All these characteristics could be used to split the classical EEG bands, especially the delta and alpha bands and be useful for physiological and pharmacological research.     

Schizotypy trait and striatal dopamine receptors in healthy volunteers

Individuals with schizotypal features exhibit cognitive, perceptual and social deficits that are similar to but less prominent than those seen in patients with schizophrenia. Dopaminergic hyperactivity in the striatum has been related to the positive symptoms of schizophrenia, and brain-imaging studies of dopamine uptake in the striatum are thought to be linked to the pathophysiological mechanisms underlying schizophrenia. The aim of this study was to investigate whether the increased availability of striatal dopamine (DA) D(2/3) receptors is related to elevated levels of schizotypal features in healthy individuals. The Schizotypal Personality Questionnaire (SPQ) was administered to 55 healthy volunteers. The availability of their striatal DA D(2/3) receptors was analysed using [(123)I] iodobenzamide single photon emission computed tomography (SPECT). Although the SPQ total scores showed no correlation with the availability of total (left and right) striatal DA D(2) receptors, the SPQ disorganised subscale scores were positively correlated with the availability of right striatal DA D(2/3) receptors. Our findings demonstrated that the availability of striatal DA D(2/3) receptors may be associated with schizotypal features in healthy volunteers.     

Diurnal periodicity of lateral asymmetries of the visual evoked potential in healthy volunteers

Visual evoked potential (VEP) was analyzed in 24 healthy male volunteers (age: 25-35 years) between 7.00 a.m. and 4.00 p.m. to evaluate possible diurnal variation in hemispheric differences of the response to a diffuse or 1 degree flash and checkerboard pattern-reversal (stimulation: binocular). VEP was recorded over O1-A1 and O2-A2, and 64 exposures were averaged during each session. After diffuse and 1 degree flash stimulation the amplitudes of early components (latencies less than 140 ms) were higher over the right hemisphere (O2-A2) than over the left (O1-A1) in the morning. These differences disappeared during the afternoon. Late components (latencies greater than 250 ms) exhibited higher amplitudes over the left than over the right hemisphere during the whole experiment. With checkerboard pattern-reversal stimulation such a time-dependent change in the amplitudes of VEP between both hemispheres was not measurable.     

Trait Openness and serotonin 2A receptors in healthy volunteers: A positron emission tomography study

Recent research found lasting increases in personality trait Openness in healthy individuals and patients after administration of the serotonin 2A receptor (5‐HT_2AR) agonist psilocybin. However, no studies have investigated whether 5‐HT_2AR availability as imaged using positron emission tomography (PET) is associated with this trait. In 159 healthy individuals (53 females), the association between 5‐HT_2AR binding in neocortex imaged with [¹⁸F]altanserin or [¹¹C]Cimbi‐36 PET and personality trait Openness was investigated using linear regression models. In these models the influence of sex on the association was also investigated. Trait Openness was assessed with the NEO Personality Inventory‐Revised. No significant associations between neocortical 5‐HT_2AR binding and trait Openness were found for [¹⁸F]altanserin (p = 0.5) or [¹¹C]Cimbi‐36 (p = 0.8). Pooling the data in a combined model did not substantially change our results (p = 0.4). No significant interactions with sex were found (p > 0.35). Our results indicate that differences in 5‐HT_2AR availability are not related to variations in trait Openness in healthy individuals. Although stimulation of the 5‐HT_2AR with compounds such as psilocybin may contribute to long‐term changes in trait Openness, there is no evidence in favor of an association between 5‐HT_2AR and trait Openness.     

Platelet alpha 2-adrenergic receptors in depressed patients and healthy volunteers: the effects of desipramine.

Binding parameters (Bmax and Kd) of alpha 2-adrenergic receptors were studied in platelets from 14 depressed patients and 18 control subjects. Using 3H-clonidine (a partial alpha 2-adrenergic agonist) as the ligand and membranes, prepared from platelets isolated under physiological conditions, we found no significant differences in Bmax and Kd between medication free patients and control subjects. Platelet binding parameters in the depressed patients did not correlate with plasma levels of norepinephrine, epinephrine or MHPG. Age had a significant positive effect on platelet alpha 2-adrenergic receptor Bmax in both groups, and may have masked the patient-control differences. Treatment with desipramine for 28 days had no effect on the binding parameters in depressed patients when compared to pretreatment values. Adding desipramine to platelets of control subjects 'in vitro' did also not affect binding parameters. Our findings suggest that receptor binding studies with a partial alpha 2-adrenergic agonist in platelet membranes are not a useful model to test the hypothesis of a central supersensitive adrenergic system in depression.     

Influence of ethanol on CD2 receptors of lymphocytes in alcohol dependent inpatients and healthy individuals

Tinnitus has been associated with psychiatric disorders and more recently diagnostic tools have been used in a systematic manner. In the present study, we administered the World Health Organisation's Composite International Diagnostic Interview – Short form (CIDI-SF) in a computerized Internet-based version to a self-selected sample of tinnitus patients (n=48). Using the cut-off for ‘probable case’ (12-month prevalence), 69% of the tinnitus patients fulfilled the criteria for depression, 60% for generalized anxiety disorder, 83% for specific phobia, 67% for social phobia, 58% for agoraphobia, 21% panic attack, 83% obsessive–compulsive disorder, 2% alcohol dependence and 0% drug dependence. Decreased percentages were found for depression (4%), specific phobia (62%) and social phobia (27%) when applying a more conservative criteria (maximum case criteria). In conclusion, the findings suggest that the Internet version of CIDI-SF can be used as a screening tool for psychiatric disturbance in somatic patients, but that diagnostic criteria need to be adjusted for Internet use.     

Diurnal variation of pain perception and heart rate in the human tourniquet pain model in healthy volunteers

The diurnal variation of pain threshold was studied in 13 healthy volunteers (age: 21 - 27 ys) using the tourniquet pain model. A tourniquet was inflated above systolic blood pressure for 1 minute and pain scores and heart rate were recorded at 0.5, 1.0, 1.5 and 2.0 minutes. The test was repeated during a study day at 6.00 h, 12.00 h, 18.00 h and 24.00 h. Significant differences of pain scores between clocktimes were found 1 minutes after inflation and after 1.5 minutes with regard to heart rate. Generally, the highest pain scores were found at 24.00 h.     

T cell activation in Guillain-Barré syndrome and in MS: elevated serum levels of soluble IL-2 receptors

Guillain-Barré syndrome (GBS), chronic idiopathic demyelinating polyradiculoneuropathy (CIDP), and multiple sclerosis (MS) are disorders with presumed immunopathogenesis. To obtain evidence for T cell activation, we determined serum concentrations of soluble interleukin-2 receptors (sIL-2 R) in 50 patients with GBS, 24 with CIDP, and 54 with MS. Both in GBS and clinically active MS sIL-2 R levels were markedly increased compared with those in patients with other neurologic diseases. Four of 24 CIDP patients had abnormally increased sIL-2 R concentrations. sIL-2 R concentrations decreased with clinical improvement in serial samples taken from GBS patients, but were not otherwise correlated with disease severity. These data establish that T cells are activated in GBS and some patients with CIDP, and corroborate earlier evidence that activated T cells are circulating in the blood of MS patients.     

细胞因子IL-2、IL-10、TNF-α在小鼠单纯疱疹病毒性脑炎中的表达

目的检测细胞因子IL-2、IL-10、TNF-α在单纯疱疹病毒性脑炎(HSE)中的表达和变化,探讨细胞因子IL-2、IL-10、TNF-α在HSVE发病机制中的作用.方法使用逆转录-聚合酶链反应(RT-PCR)检测颅内感染单纯疱疹病毒1型(HSV1)的小鼠在感染后及使用无环鸟苷(ACV)治疗后细胞因子IL-2、IL-10、TNF-α变化及病理变化.结果HSV1感染后出现脑内出血坏死性的病理改变,IL-2、IL-10、TNF-α均明显上升;无环鸟苷治疗好转后脑内病理变化改善,IL-2保持稳定,IL-10继续上升,TNF-α显著下降.结论在小鼠HSVF急性期TH1型及TH2型反应同时被激活,发挥抗病毒作用,并以TH1型反应为主;在HSVE恢复期以TH2型反应为主,并抑制体内免疫反应的扩大;3种细胞因子的动态变化反映出机体免疫调节的动态平衡,并可反映HSVE的预后,早期应用ACV治疗HSVE确有极其明显的抗病毒治疗作用.     

Endotoxin-induced changes in food consumption in healthy volunteers are associated with TNF-alpha and IL-6 secretion

This study examined the effects of endotoxin administration on food and water consumption in humans, and the associations between these changes and endotoxin-induced secretion of cytokines, cortisol, and fever. Twenty healthy male volunteers received an i.v. injection of Salmonella abortus equi endotoxin (0.8 ng/kg) or saline in two experimental sessions. Blood samples were collected hourly, and rectal temperature was monitored continuously. Food consumption was significantly reduced at 0-4 h and significantly elevated at 4-5 h after the endotoxin injection. Endotoxin administration had no significant effect on water consumption. Endotoxin-induced secretion of TNF-alpha and IL-6 was positively associated with the decrease in food consumption (r=0.61 and 0.68), and negatively associated with the rebound increase in food consumption (r=-0.53 and -0.45). Neither the febrile response, nor the secretion of cortisol was associated with the changes in food consumption. These results suggest that TNF-alpha and IL-6 are involved in endotoxin-induced anorexia in humans.     

Yohimbine premedication and 35% CO2 vulnerability in healthy volunteers

Summary A group of 20 healthy volunteers underwent a 35% carbon dioxide / 65% oxygen air-placebo controlled challenge test twice, premedicated 1 h before with either 20 mg yohimbine or placebo, following a double-blind randomized crossover design. Contrary to expectation the anxiety response to carbon dioxide was not higher when premedicated with yohimbine compared to premedication with placebo. Possible implications of this finding are discussed, with reference to general chemical models of panic.     

Soluble IL-2 receptors in acute and subacute encephalitis

Elevated levels of soluble interleukin-2 receptors were present in the serum from patients with acute primary and postinfectious encephalitis and subacute sclerosing panencephalitis. In addition, soluble interleukin-2 receptors were detected in the cerebrospinal fluid from patients with acute primary encephalitis. Their presence in the cerebrospinal fluid was not explained by damage to the blood-brain barrier and our data attest to their local origin. This suggests that it may be possible in certain neurological diseases to detect cerebral T-lymphocyte activation through a specific marker in the cerebrospinal fluid.     

Neural activities of IL-6-type cytokines often depend on soluble cytokine receptors

Cytokines of the interleukin-6 (IL-6) family participate in regulatory and inflammatory processes within the nervous system. IL-6, ciliary neurotrophic factor (CNTF) and IL-11 act via specific membrane receptors which, together with their ligands, associate with signal-transducing receptor subunits thereby initiating cytoplasmic signalling. Cells which only express signal-transducing receptor subunits but no ligand binding subunits for IL-6, CNTF and IL-11 are refractory to these cytokines. An unusual feature of the IL-6 cytokine family is that the soluble forms of the ligand binding receptor subunits generated by one cell type in complex with their ligands can directly stimulate the signal-transducing receptor subunits on different cell types which lack ligand binding receptor subunits. This process has been named transsignalling. This article focuses on the importance of transsignalling events in neuronal differentiation and survival responses.     

Diurnal patterns of serotonin, 5-hydroxyindoleacetic acid, tryptophan and fibrinolytic activity in blood of depressive patients and healthy volunteers.

Diurnal changes of serotonin-related factors in whole blood and fibrinolytic activity were determined in depressed patients and healthy controls. Whole blood serotonin concentration of depressed patients showed marked changes throughout daytime, with maximum values in the evening and lowest values in the morning, whereas its metabolite 5-HIAA followed a contrary pattern. The circadian rhythm of 5-HT and 5-HIAA in the control group was quite different from depressed patients. Plasma levels of tPA decreased from 12:30 to 16:30. Concentrations of free plasminogen activator inhibitor (PAI-1) and complex of tPA-PAI-1 decreased from 8:30 to 16:30. Plasma levels of total PAI-1 decreased from 8:30 to 16:30. Plasma levels of the fibrinolytic parameters may be lower in depressive patients than in normal controls. These results support the changes in the circadian rhythm of serotonin and its related substances in the blood of depressive patients.     

Diurnal rhythm in anticoagulant effect of heparin during a low dose constant rate infusion. A study in healthy volunteers.

The objective of the study was to investigate possible diurnal rhythms in coagulation tests during a continuous intravenous infusion of unfractionated heparin. Six volunteers participated in the study, which was divided in a treatment (500 U heparin/h for 30 h) and a control experiment. Under basal conditions, no rhythm was found in coagulation tests. During heparin treatment, APTT, thrombin clotting time and anti-Xa activity showed a greater anticoagulant effect at night, with a striking decrease in the morning. In a search for the explanation of this phenomenon we looked for diurnal variations in the urinary excretion of heparin, in the plasma concentrations of antithrombin III and platelet factor 4, and in the effect of heparin added to the plasma samples in vitro. None of these studies provided the explanation.     

Diurnal and seasonal variations in human platelet serotonin in man

Summary Platelet serotonin (5-HT) was found to be an individually constant parameter correlating with the uptake of exogenous 5-HT. A pronounced diurnal pattern of 5-HT, with a minimum in the afternoon and higher values in the morning and evening, was similar to the diurnal variations in plasma free tryptophan. Platelet 5-HT was significantly higher at 8 a.m. than 4 p.m. in spring but no longer in autumn, and was similar in both men and women. It appeared that peripheral diurnal variations in 5-HT were opposite in phase to the central 5-HT rhythm.