Biomedical subjects

Michael Maes

Publications and source records attributed to Michael Maes.

8 recordsLinked to original sources

PubMed2002

Depressive and anxiety symptoms in the early puerperium are related to increased degradation of tryptophan into kynurenine, a phenomenon which is related to immune activation.

There is now some evidence that i) the availability of plasma tryptophan, the precursor of serotonin, is significantly lower in pregnant women at the end of term and the first few days after delivery than in nonpregnant women; and ii) both pregnancy and the early puerperium are accompanied by activation of the inflammatory response system. The aims of the present study were to examine the effects of pregnancy and delivery on plasma kynurenine, a major tryptophan catabolite synthesized after induction of indoleamine-2, 3 dioxygenase (IDO) by pro-inflammatory cytokines. We measured plasma kynurenine and tryptophan and immune markers, such as serum interleukin-6 (IL-6), IL-8 and the leukemia inhibitory factor-receptor (LIF-R) in healthy, nonpregnant and pregnant women at the end of term and one and three days after delivery. Plasma kynurenine was significantly lower in pregnant women at the end of term than in nonpregnant women, findings which may be attributed to lower plasma tryptophan at the end of term. The kynurenine/tryptophan (K/T) quotient was significantly higher in the pregnant women at the end of term and in the early puerperium than in nonpregnant women. In the early puerperium there was a significant increase in plasma kynurenine and the K/T quotient. The increases in plasma kynurenine and the K/T quotient were significantly more pronounced in women whose anxiety and depression scores significantly increased in the puerperium. The changes from the end of term to the early puerperium in plasma kynurenine and the K/T quotient were significantly related to those in the immune markers. It is concluded that 1) lower plasma kynurenine at the end of term is the consequence of lower plasma tryptophan; 2) the increased K/T quotient at the end of term and in the early puerperium indicates inflammation-induced degradation of tryptophan along the kynurenine pathway; and 3) that depressive and anxiety symptoms in the early puerperium are (causally) related to an increased catabolism of tryptophan into kynurenine, a phenomenon which probably results from immune activation.

Adult↗

PubMed2002

Increased serum interleukin-8 and interleukin-10 in schizophrenic patients resistant to treatment with neuroleptics and the stimulatory effects of clozapine on serum leukemia inhibitory factor receptor.

There is now evidence that schizophrenia may be accompanied by an activation of the monocytic and T-helper-2 (Th-2) arms of cell-mediated immunity (CMI) and by various alterations in the Th-1 arm of CMI. There is also evidence that repeated administration of typical and atypical antipsychotics may result in negative immunomodulatory effects. This study was carried out to examine (1) the serum concentrations of interleukin-8 (IL-8), IL-10, the soluble CD8 (sCD8) and the leukemia inhibitory factor receptor (LIF-R) in nonresponders to treatment with typical neuroleptics as compared with normal volunteers and responders to treatment; and (2) the effects of atypical antipsychotics on the above immune variables. The latter were determined in 17 nonresponders to treatment with neuroleptics and in seven normal volunteers and 14 schizophrenic patients who had a good response to treatment with antipsychotic agents. The nonresponders had repeated measurements of the immune variables before, and 2 and 4 months after treatment with clozapine or risperidone. Serum IL-8 and IL-10 were significantly higher in schizophrenic patients than in normal controls. The serum concentrations of the sCD8 were significantly increased 2 months, but not 4 months, after starting treatment with atypical antipsychotics. Serum LIF-R concentrations were significantly increased 2 and 4 months after starting treatment with atypical antipsychotics. It is concluded that: (1) schizophrenia is characterized by an activation of both pro-inflammatory and anti-inflammatory aspects of cell-mediated immunity; (2) prolonged treatment with atypical antipsychotics may increase the anti-inflammatory capacity of the serum in schizophrenic patients by increasing serum LIF-R concentrations; and (3) short-term treatment with clozapine may induce signs of immune activation which disappear upon prolonged treatment.

Adult↗

PubMed2002

Increased depressive ratings in patients with hepatitis C receiving interferon-alpha-based immunotherapy are related to interferon-alpha-induced changes in the serotonergic system.

There is now evidence that repeated administration of interferon-alpha (IFN-alpha) to patients with chronic active hepatitis and cancers induces depressive symptoms. There is also evidence that induction of the cytokine network modulates the serotonergic system and that major depression is related to activation of the cytokine network and disturbances in the serotonergic metabolism. The aims of this study were to examine the effects of IFN-alpha-based immunotherapy on the development of depressive symptoms in relation to its effects on plasma tryptophan and kynurenine and serum serotonin (5-HT). Eighteen patients affected by chronic active hepatitis C were treated with IFN-alpha (3-6 million units subcutaneously three to six times a week for 6 months) and had measurements of the previous parameters before starting immunotherapy and 2, 4, 16, and 24 weeks later. Severity of depression and anxiety were measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Rating Scale for Anxiety (HAM-A) scale, respectively. Immunochemotherapy with IFN-alpha (1) significantly increased the MADRS and HAM-A scores and serum kynurenine concentrations and (2) significantly reduced plasma tryptophan and serum 5-HT concentrations. IFN-alpha-based immunotherapy significantly increased the kynurenine per tryptophan quotient, which estimates the activity of indoleamine 2,3-dioxygenase, the major tryptophan-catabolizing enzyme, which is induced by IFNs. There are significant relationships between the IFN-alpha-induced changes in the MADRS score and serum kynurenine (positive) and 5-HT (negative) concentrations. Immunotherapy with IFN-alpha significantly increases the severity of depressive symptoms. The latter is related to changes in the serotonergic system, such as depletion of serum 5-HT and induction of the catabolism of tryptophan to kynurenine. It is suggested that the IFN-alpha-induced changes in the serotonergic turnover could play a role in the development of IFN-alpha-induced depressive symptoms.

Adult↗

PubMed2002

Activation of the inflammatory response system in autism.

BACKGROUND/AIM: There is now some evidence that autism may be accompanied by abnormalities in the inflammatory response system (IRS). Products of the IRS, such as proinflammatory cytokines, may induce some of the behavioral symptoms of autism, such as social withdrawal, resistance to novelty and sleep disturbances. The main aim of the present study was to examine whether autism is accompanied by an activation of the IRS. METHODS: We measured the production of interleukin (IL)-6, IL-10, the IL-1 receptor antagonist (IL-1RA), interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha by whole blood and the serum concentrations of IL-6, the IL-2 receptor (IL-2R) and IL-1RA. RESULTS: This study showed a significantly increased production of IFN-gamma and IL-1RA and a trend toward a significantly increased production of IL-6 and TNF-alpha by whole blood of autistic children. There were no significant differences in the serum concentrations of IL-6, IL-2R and IL-1RA between autistic and normal children. CONCLUSIONS: These results suggest that autism may be accompanied by an activation of the monocytic (increased IL-1RA) and Th-1-like (increased IFN-gamma) arm of the IRS. It is hypothesized that increased production of proinflammatory cytokines could play a role in the pathophysiology of autism.

Adolescent↗

PubMed2001

Biography.

Explore the source record for details and available documents.

Journal Article↗

PubMed2000

Negative immunoregulatory effects of noradrenaline through alpha2-adrenoceptor activation.

BACKGROUND: There are some reports that catecholamines and beta-adrenoceptor agonists may suppress some immune functions. OBJECTIVES: The present study was carried out in order to examine the effects of noradrenaline (10-5 M, 10-6 M and 10-7 M), yohimbine (10-5 M, 10-6 M and 10-7 M), an alpha2-adrenoceptor antagonist, and clonidine (105 M, 10-6 M and 10-7 M), an alpha2-adrenoceptor agonist, on the stimulated production of interferon-gamma (IFNgamma), a pro-inflammatory cytokine, and interleukin-10 (IL-10), an immuno-inhibitory cytokine. DESIGN: We measured the in vitro production of IFNgamma and IL-10 by stimulated, diluted whole blood of 16 normal volunteers. The IFNgamma/IL-10 production ratio was computed since this ratio reflects the pro- versus anti-inflammatory capacity of the cultured whole blood. RESULTS: We found that 1) noradrenaline, 10-5 M, 10-6 M, and 10-7 M, significantly suppressed the production of IFNgamma and that noradrenaline, 10-5 M, significantly enhanced the production of IL-10. Clonidine, 10-5 M and 10-7 M, significantly suppressed the production of IFNgamma. Noradrenaline, 10-5 M and 10-6 M, and clonidine, 10-5 M, significantly suppressed the IFNgamma/IL-10 production ratio. There were no significant effects of yohimbine on IFNgamma or IL-10 production. CONCLUSIONS: 1) noradrenaline has significant negative immunoregulatory effects in humans through enhancing the production of IL-10 and suppressing that of IFNgamma; and 2) the suppression of the production of IFNgamma is in part related to alpha2-adrenoceptor activation.

Journal Article↗

PubMed2000

Relationships of climatic data to immune and hematologic variables in normal human.

OBJECTIVES: The purpose of this study was to examine the relationships between climatic and immune or hematologic variables in the peripheral blood of normal human. METHODS: Twenty-six normal volunteers gave blood samples monthly during one calendar year for flow cytometric assays of peripheral blood mononuclear cells (PBMC) and assays of red blood cell (RBC)- and platelet-related variables. Time relationships between the weather and immune or hematologic variables were investigated by means of multiple regression and bivariate cosinor analyses. RESULTS: Highly significant relationships were found among number and percentage of neutrophils, lymphocytes, CD4+, CD8+, CD25+ (interleukin-2-receptor bearing lymphocytes), CD20+ B lymphocytes, number of platelets and RBC, hemoglobin (Hb), mean corpuscular (MC) volume, MC Hb, MC Hb concentration, mean platelet volume or plasma fibrinogen levels and ambient temperature, sunlight duration, air pressure, wind speed, relative humidity, and rainfall duration/day. An important part of the variability in the immune and hematologic variables could be explained by the composite effects of contemporaneous and lagged climatic variables. Common seasonal rhythms were detected in the time series of the above immune/hematologic and sun insolation variables, such as ambient temperature. CONCLUSIONS: The results suggest that i) short-term fluctuations in atmospheric activity modulate immune and hematologic features in the peripheral blood of normal human; and ii) the seasonal rhythms observed in immune/hematologic variables may be entrained by the seasonal rhythms in ambient temperature.

Journal Article↗

PubMed1999

Activation of the inflammatory response system: A new look at the etiopathogenesis of major depression.

Major depression is accompanied by various direct and indirect indicators of a moderate activation of the inflammatory response system (IRS). Increased production of proinflammatory cytokines, such as interleukin-1 (IL-1), IL-6 and interferon (IFNgamma), may play a crucial role in the immune and acute phase response in depression. Lower serum zinc and changes in the erythron are indirect indicators of IRS activation in depression. The reciprocal relationships between IRS activation and hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity, alterations in HP thyroid (HPT)-axis function and the availability of tryptophan to the brain led us to hypothesize that these neuroendocrine changes in depression are indicators of IRS activation and that a combined dysregulation of the IRS, the turnover of serotonin (5-HT) and the HPA-axis is an integral component of depression. The IRS activation model of depression provides an explanation for the psycho-social (external stress) as well as organic (internal stress) etiology of major depression. Antidepressive treatments with various antidepressive agents, including SSRIs, tricyclic and heterocyclic antidepressants, have in vivo and in vitro negative immunoregulatory effects, suggesting that their antidepressant efficacy may be attributed, in part, to their immune effects.

Journal Article↗