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Biomedical subjects

A Kavelaars

Publications and source records attributed to A Kavelaars.

At least 37 records · Page 2Linked to original sources
PubMed2000

High nocturnal melatonin in adolescents with chronic fatigue syndrome.

Decreased quality of sleep is frequently reported by chronic fatigue syndrome (CFS) patients. The pineal hormone melatonin is involved in regulation of sleep. We analyzed the nocturnal rise in melatonin in 13 adolescent CFS patients and 15 healthy age-matched controls. Saliva samples were collected at hourly intervals between 1700 and 0200 h. Nocturnal saliva melatonin levels were significantly higher in CFS patients, compared with controls, at midnight, 0100 h, and 0200 h (P < 0.001). No differences were observed in timing of melatonin increase in saliva between patients and controls. Time of sleep onset and duration of sleep did not differ significantly between patients and controls. However, all CFS patients and only one of the controls in our study group reported unrefreshing sleep. Our data demonstrate that sleep problems in adolescents with CFS are associated with increased melatonin levels during the first part of the night. Based on these data, we suggest that there is no indication for melatonin supplementation in adolescents with CFS.

Adolescent↗
PubMed2000

Disturbed neuroendocrine-immune interactions in chronic fatigue syndrome.

The present study was designed to investigate the interaction between neuroendocrine mediators and the immune system in chronic fatigue syndrome (CFS). We examined the sensitivity of the immune system to the glucocorticoid agonist dexamethasone and the beta2-adrenergic agonist terbutaline in 15 adolescent girls with CFS and 14 age- and sex-matched controls. Dexamethasone inhibits T-cell proliferation in healthy controls and in CFS patients. However, the maximal effect of dexamethasone on T-cell proliferation is significantly reduced in CFS patients as compared with controls. The beta2-adrenergic receptor agonist terbutaline inhibits tumor necrosis factor-alpha production and enhances interleukin-10 production by monocytes. Our data demonstrate that the capacity of a beta2-adrenergic agonist to regulate the production of these two cytokines is also reduced in CFS patients. We did not observe differences in baseline or CRH-induced cortisol and ACTH between CFS patients and controls. Baseline noradrenaline was similar in CFS and controls, whereas baseline adrenaline levels were significantly higher in CFS patients. We conclude that CFS is accompanied by a relative resistance of the immune system to regulation by the neuroendocrine system. Based on these data, we suggest CFS should be viewed as a disease of deficient neuroendocrine-immune communication.

Adolescent↗
PubMed1999

Neuroendocrine mediators up-regulate alpha1b- and alpha1d-adrenergic receptor subtypes in human monocytes.

Beta2- and alpha2-adrenergic receptors (AR) are thought to be the main AR subtypes to exert the effects of catecholamines on the immune system. However, in the present study, we demonstrate that another subtype of AR can be induced in human monocytes. Expression of alpha1b- and alpha1d-AR mRNA can be obtained by culturing freshly isolated human peripheral blood monocytes with the neuroendocrine mediators dexamethasone or the beta2-AR agonist terbutaline. Using the human monocytic cell line THP-1, we demonstrate that increased levels of alpha1b- and alpha1d-mRNA are accompanied by increased levels of receptor protein as determined by Western blot analysis and radioligand binding assays. This study describes for the first time regulated expression of alpha1-AR subtypes in human monocytes.

Adrenergic beta-Agonists↗
PubMed1999

Individual behavioral characteristics of wild-type rats predict susceptibility to experimental autoimmune encephalomyelitis.

Neuroendocrine-immune interactions are thought to be important in determining susceptibility to autoimmune disease. Animal studies have revealed that differences in susceptibility to experimental autoimmune encephalomyelitis (EAE) are related to reactivity in the hypothalamo-pituitary-adrenal axis. It is known that there is a close relation between neuroendocrine parameters and behavioral characteristics, suggesting that behavior and disease susceptibility may be associated. In the present study we investigated whether behavioral characteristics of wild-type rats are related to susceptibility to disease. We show here that the latency of the animal to attack an intruder correlates significantly with the EAE disease score: animals that do not attack the intruder during the test period are more resistant to the disease than animals with short attack latency times. These data, obtained in an unselected strain of wild-type rats, demonstrate that behavioral response patterns of individual animals can in part predict susceptibility to autoimmune disease.

Aggression↗
PubMed1999

Patients with systemic lupus erythematosus differ from healthy controls in their immunological response to acute psychological stress.

Clinical observations suggest that psychological stress induces exacerbation of disease activity in patients with systemic lupus erythematosus (SLE). In order to determine whether SLE patients differ from healthy controls in their stress response, we analyzed heart rate, blood pressure, catecholamine concentration, lymphocyte subpopulations, natural killer (NK) cell activity, and expression of beta-adrenoceptors on PBMC before, immediately after, and 1 h after a public speaking task in 15 SLE patients and 15 healthy subjects. Both groups demonstrated similar psychological, cardiovascular, and neuroendocrine responses to acute stress. However, natural killer (CD16(+)/CD56(+)) cell numbers transiently increased after stress exposure, with significantly less pronounced changes in SLE patients. In addition, NK activity increased in healthy controls (n = 8) but not in SLE patients (n = 4) after acute stress. Furthermore, the number of beta(2)-adrenoceptors on PBMC significantly increased only in healthy subjects (n = 8) after stress but not in SLE patients (n = 7). These data indicate that SLE patients differ from healthy controls in stress-induced immune responses.

Acute Disease↗
PubMed1999

Pro- and anti-inflammatory cytokine patterns during and after cardiac surgery in young children.

UNLABELLED: The systemic inflammatory response that occurs after cardiopulmonary bypass shows many changes similar to those seen in sepsis. The mechanisms for these changes have been attributed to cellular and humoral activation, such as increased secretion of cytokines and complement. The aim of our study was to investigate the cytokine pattern of pro- and anti-inflammatory cytokines in young children during and after bypass surgery. Nineteen children undergoing either septal defect correction (n = 12), or more complex surgery (n = 7), were prospectively included in this study. There were significant higher pre-operative levels of circulating cytokines in the latter group. Cardiopulmonary bypass surgery induced in both groups a rise in circulating cytokine levels and a sharp decline in the capacity of the leucocytes to secrete interleukines-6 and -8 in response to ex vivo stimulation with lipopolysaccharide. Ex vivo production of interleukine-1 receptor antagonist was slightly attenuated by the procedure. CONCLUSIONS: The downregulation of ex vivo pro- and, to some extent, anti-inflammatory cytokine production may be a reflection of a cellular stress response, induced by anaesthesia, cardiopulmonary bypass and surgery.

Anti-Inflammatory Agents↗
PubMed1999

The importance of being receptive.

Neuroendocrine system and immune system can communicate via the use of soluble mediators like hormones, neurotransmitters and cytokines. The level of mediators secreted by either of these systems creates the milieu in which immune and neuroendocrine responses take place. For adequate communication between the systems, receptors for hormones, neurotransmitters and cytokines are required. This review describes the role of regulated expression and function of receptors for hormones and neurotransmitters within the immune system in neuroendocrine-immune communication.

Adrenergic beta-Agonists↗
PubMed1999

Peripheral blood cytokine responses and disease severity in respiratory syncytial virus bronchiolitis.

The role of cellular immunity in disease severity in respiratory syncytial virus (RSV) bronchiolitis is largely unknown. This study investigated the association between disease severity and systemic cytokine responses in hospitalized ventilated and nonventilated RSV bronchiolitis patients. In whole blood cultures stimulated with phytohaemagglutinin (PHA), lymphoproliferative responses and interferon (IFN)-gamma and interleukin (IL)-4 production during acute illness were measured. In addition, plasma cytokines were measured. Measurements were repeated in the convalescent phase, 3-4 weeks after admission. Fifty patients were included. The median age in ventilaled patients was significantly lower than in nonventilated patients (1 versus 4 months, p<0.05). In comparison with nonventilated patients, the ventilated patients had significantly lower lymphoproliferative responses and a lower production of IFN-gamma and IL-4. In fact, IFN-gamma and IL-4 production in ventilated patients was almost completely undetectable. Plasma IL-8 levels in ventilated patients were significantly higher than in nonventilated patients. In the convalescent phase, lymphoproliferative and cytokine responses as well as plasma IL-8 levels were normal in both patient groups. Since RSV bronchiolitis is associated with the subsequent development of asthma, the possible skewing of the T-helper (Th1/Th2) cytokine balance was investigated. This was found neither in the acute nor in the convalescent phase. In conclusion, the data indicate that depressed lymphocyte function and elevated plasma interleukin-8 levels are markers of severe disease. It is suggested that age and maturation related immune mechanisms could explain the occurrence of severe respiratory syncytial virus bronchiolitis requiring mechanical ventilation in young infants.

Antibodies, Viral↗
PubMed1999

Naturally induced secretions of the potato cyst nematode co-stimulate the proliferation of both tobacco leaf protoplasts and human peripheral blood mononuclear cells.

Naturally induced secretions from infective juveniles of the potato cyst nematode Globodera rostochiensis co-stimulate the proliferation of tobacco leaf protoplasts in the presence of the synthetic phytohormones alpha-naphthaleneacetic acid (NAA) and 6-benzylaminopurine (BAP). With the use of a protoplast-based bioassay, a low-molecular-weight peptide(s) (< 3 kDa) was shown to be responsible for the observed effect. This mitogenic oligopeptide(s) is functionally dissimilar to auxin and cytokinin and, in addition, it does not change the sensitivity of the protoplasts toward these phytohormones. In combination with the mitogen phytohemagglutinin (PHA), cyst nematode secretions also co-stimulated mitogenesis in human peripheral blood mononuclear cells (PBMC). The stimulation of plant cells isolated from nontarget tissue--these nematodes normally invade the roots of potato plants--suggests the activation of a general signal transduction mechanism(s) by an oligopeptide(s) secreted by the nematode. Whether a similar oligopeptide-induced mechanism underlies human PBMC activation remains to be investigated. Reactivation of the cell cycle is a crucial event in feeding cell formation by cyst nematodes. The secretion of a mitogenic low-molecular-weight peptide(s) by infective juveniles of the potato cyst nematode could contribute to the redifferentiation of plant cells into such a feeding cell.

Adenine↗
PubMed1999

Decreased expression and activity of G-protein-coupled receptor kinases in peripheral blood mononuclear cells of patients with rheumatoid arthritis.

Beta2-Adrenergic and chemokine receptor antagonists delay the onset and reduce the severity of joint injury in rheumatoid arthritis. beta2-Adrenergic and chemokine receptors belong to the G-protein-coupled receptor family whose responsiveness is turned off by the G-protein-coupled receptor kinase family (GRK-1 to 6). GRKs phosphorylate receptors in an agonist-dependent manner resulting in receptor/G-protein uncoupling via subsequent binding of arrestin proteins. We assessed the activity of GRKs in lymphocytes of rheumatoid arthritis (RA) patients by rhodopsin phosphorylation. We found a significant decrease in GRK activity in RA subjects that is mirrored by a decrease in GRK-2 protein expression. Moreover, GRK-6 protein expression is reduced in RA patients whereas GRK-5 protein levels were unchanged. In search of an underlying mechanism, we demonstrated that proinflammatory cytokines induce a decrease in GRK-2 protein levels in leukocytes from healthy donors. Since proinflammatory cytokines are abundantly expressed in RA, it may provide an explanation for the decrease in GRK-2 expression and activity in patients. No changes in beta2-adrenergic receptor number and Kd were detected. However, RA patients showed a significantly increased cAMP production and inhibition of TNF-alpha production by beta2-adrenergic stimulation, suggesting that reduced GRK activity is associated with increased sensitivity to beta2-adrenergic activation.

Adrenergic beta-Agonists↗
PubMed1999

Altered immune function in human newborns after prenatal administration of betamethasone: enhanced natural killer cell activity and decreased T cell proliferation in cord blood.

During the course of human pregnancy, glucocorticoid (GC) treatment is given when preterm delivery is expected. This treatment is successful in stimulating the development of the fetal lung. However, in animal studies, a number of side effects of perinatal GC treatment have been described. The aim of the present study was to evaluate in humans the effects of antenatal GC treatment on development of the immune system. In addition, we examined the development of immune reactivity in infants born preterm and at term who did not receive GC treatment antenatally. We tested mitogen-induced T cell proliferation, natural killer cell activity, and lipopolysaccharide-induced IL-6 production in cord blood samples. We found that there is a significant effect of gestational age on the capacity of T cells to proliferate and of natural killer cells to kill K562 tumor cells. The capacity to produce IL-6 does not change between gestational age 26 and 41 wk. Moreover, our results show that antenatal treatment with GC does have immunomodulatory effects: T cell proliferation is decreased in infants born very preterm (gestational age 26-31 wk) as well as in infants born between 32 and 36 wk of gestation. In contrast, the activity of natural killer cells is only increased in GC-treated infants born between 26 and 31 wk. We did not observe a significant effect of antenatal GC treatment on the capacity to produce IL-6.

Betamethasone↗
PubMed1998

The reactivity of the cardiovascular system and immunomodulation by catecholamines in juvenile chronic arthritis.

Juvenile chronic arthritis is associated with clinical symptoms indicating that there is a dysregulation of the sympathetic nervous system (SNS). Our data show that patients with juvenile chronic arthritis have an altered function of the SNS associated with increased central noradrenergic outflow, presumably leading to increased vasoconstriction, resulting in a decreased response to an orthostatic stressor. We also investigated the consequences of the altered reactivity of SNS for the reactivity of the immune system to mediators of the sympathetic nervous system and to glucorticoids. It appeared that leukocytes of these patients have an altered response to catecholamines. Triggering of the beta 2-adrenergic receptor leads to reduced cAMP responses that are due to the higher rate of cAMP degradation. In addition, catecholamines induce the production of IL-6 by leukocytes of these patients, via triggering of alpha 1-adrenergic receptors. Healthy controls do not express functional alpha 1-adrenergic receptors.

Animals↗
PubMed1998

Role of endogenous pro-enkephalin A-derived peptides in human T cell proliferation and monocyte IL-6 production.

In this paper, we describe that met-enkephalin and/or enkephalin-containing intermediary peptides of the prohormone pro-enkephalin A are produced and secreted by human peripheral blood T cells and monocytes. The peptides are produced after stimulation with the mitogenic monoclonal antibodies anti-CD2.1/2.2 and anti-CD28. In monocytes, enkephalin synthesis was induced by stimulation with lipopolysaccharide. We demonstrate here that these immune cell-derived enkephalins play an important regulatory role in the immune response. By using an anti-sense oligonucleotide strategy we could block the production of enkephalins. Blockade of the production of met-enkephalin and enkephalin-containing intermediary peptides resulted in enhancement of the proliferative T cell response and inhibition of monocyte IL-6 secretion. In vitro reconstitution of the anti-sense treated cultures with synthetic met-enkephalin or the delta-type specific opioid receptor agonist deltorphin could reverse inhibition of monocyte IL-6 production, suggesting that endogenous enkephalins act via membrane opioid receptors. In contrast, addition of met-enkephalin or deltorphin to the anti-sense treated T cell cultures did not have any effect on T cell proliferation.

Antibodies, Monoclonal↗
PubMed1998

Pain in childhood rheumatic arthritis.

Pain is a major symptom in chronic inflammatory arthropathies such as rheumatoid arthritis and affects the health status of arthritis patients negatively. There has been much debate about the role of pain in juvenile chronic arthritis and this review deals with the controversies about this subject. Pain in children is best understood as a multifactorial concept in which pain is the result of somatosensory, behavioural and environmental factors. The role of the different factors contributing to pain will be assessed with special reference to mechanisms relevant to children with chronic pain, the various instruments to measure pain, such as visual analogue scales and algometry, and the treatment of chronic pain in juvenile chronic arthritis. For a true understanding of chronic pain in children, these multidimensional assessments should be integrated into a biobehavioral model, by means of which a better understanding should lead to new therapeutic interventions for one of the most common symptoms of rheumatic diseases in childhood: pain.

Arthritis, Juvenile↗
PubMed1997

Apomorphine-susceptible and apomorphine-unsusceptible Wistar rats differ in their susceptibility to inflammatory and infectious diseases: a study on rats with group-specific differences in structure and reactivity of hypothalamic-pituitary-adrenal axis.

Variability in susceptibility to diseases is a well known phenomenon that has been attributed to genetic and environmental factors. At the level of the immune system, the reactivity of two types of T helper cells (Th1 and Th2 cells) plays an important role in determining disease susceptibility. Inflammatory (autoimmune) diseases are stimulated by cytokines produced by Th1 cells. Th2 cytokines stimulate antibody production (e.g., IgE) and eosinophilia as observed in allergic reactions or during parasitic infections. We describe here that the reactivity in a Th1 or a Th2 disease model significantly differs between individual rats that show group-specific differences in reactivity of the hypothalamic-pituitary-adrenal (HPA) axis, as well as in their behavioral responses to stress. We used two outbred lines of Wistar rats, apomorphine-susceptible rats that have a relatively hyperreactive HPA axis (APO-SUS) and apomorphine-unsusceptible rats that have a relatively hyporeactive HPA axis (APO-UNSUS). APO-SUS, but not APO-UNSUS, rats generated a vigorous, Th2-dependent IgE response after infection with the nematode Trichinella spiralis. In contrast, APO-UNSUS, but not APO-SUS, rats were susceptible for Th1-mediated experimental autoimmune encephalomyelitis. Investigation of cytokine responses of splenocytes revealed that the ratio of mRNA expression for Th1-derived interferon (IFN)-gamma and mRNA expression of Th2-derived interleukin-4 (IL-4) was significantly smaller in APO-SUS than in APO-UNSUS rats. In conclusion, individual differences in structure and reactivity of the neuroendocrine system co-occur with group-specific differences in susceptibility to inflammatory and infectious diseases.

Animals↗