E. Bosmans

Increased 24‐hour urinary cortisol excretion in patients with post‐traumatic stress disorder and patients with major depression, but not h patients with fibromyalgia

There is now firm evidence that major depression is accompanied by increased baseline activity of the hypothalamic‐pituitary‐adrenal (HPA) axis, as assessed by means of 24‐h urinary cortisol (UC) excretion. Recently, there were some reports that fibromyalgia and post‐traumatic stress disorder (PTSD), two disorders which show a significant amplitude of depressive symptoms, are associated with changes in the baseline activity of the HPA axis, such as low 24‐h UC excretion. The aim of the present study was to examine 24‐h UC excretion in fibromyalgia and PTSD patients compared to normal controls and patients with major depression. In the three patient groups, severity of depressive symptoms was measured by means of the Hamilton Depression Rating Scale (HDRS) score. Severity of fibromyalgia was measured using a dolorimetrically obtained myalgic score, and severity of PTSD was assessed by means of factor analytical scores computed on the items of the Composite International Diagnostic Interview (CIDI), PTSD Module. Patients with PTSD and major depression had significantly higher 24‐h UC excretion than normal controls and fibromyalgia patients. At a threshold value of ≥240 μg/24 h, 80% of PTSD patients and 80% of depressed patients had increased 24‐h UC excretion with a specificity of 100%. There were no significant differences in 24‐h UC excretion either between fibromyalgia patients and normal controls, or between patients with major depression and PTSD patients. In the three patient groups, no significant correlations were found between 24‐h UC excretion and The HDRS score. In fibromyalgia, no significant correlations were found between 24‐h UC excretion and the myalgic score. In PTSD, no significant correlations were found between 24‐h UC excretion and severity of either depression‐avoidance or anxiety‐arousal symptoms. In conclusion, this study found increased 24‐h UC excretion in patients with PTSD comparable to that in patients with major depression, whereas in fibromyalgia no significant changes in 24‐h UC were found.

Decreased serum dipeptidyl peptidase IV activity in major depression

It has been recently shown that severe depression is characterized by immune dysfunctions such as blunted mitogen-induced blast transformation, which is linked to interleukin-2 (IL-2) mechanisms, and to autoimmune responses. In order to explore one of the putative pathophysiological mechanisms underlying both factors, we have measured the predexamethasone and postdexamethasone serum dipeptidyl-peptidase IV (DPP IV) activity in depressed inpatients and normal controls. This enzyme is an important mediator of IL-2-related blast proliferation, and it may play a role in autoimmunity. We found significantly lower DPP IV levels in major depressives as compared with healthy controls, and melancholics exhibited significantly lower enzyme activity than minor depressives. There was a significant negative correlation between serum DPP IV activity and the severity of illness. However, we were unable to detect any significant relationships between DPP IV on the one hand, and mitogen-induced blast transformation, soluble IL-2 receptor accumulation in PHA culture supernatant, total number of leukocytes and lymphocytes, T lymphocytes, CD4+ and CD25+ cells, on the other. Men exhibited significantly higher serum DPP IV levels than women.

Constitutive expression of CD26/dipeptidylpeptidase IV on peripheral blood B lymphocytes of patients with B chronic lymphocytic leukaemia

SummaryWe have investigated the expression of the ectoenzyme dipeptidylpeptidase IV (DPP IV)/CD26 on lymphocytes obtained from patients with B chronic lymphocytic leukaemia (B-CLL) and compared it with healthy subjects. Using two-colour immunofluorescence analysis with CD26 and CD20 or CD23 monoclonal antibodies, CD26 was found undetectable on peripheral resting B-cells (CD20+ CD23–) from normal donors whereas it was expressed on B-cells activated in vitro with interleukin (IL)-4 and Staphylococcus aureus strain cowan I (CD20+ CD23+). The expression of CD26 on leukaemic B-cells (CD20+ CD23+) was clearly induced in 22 out of 25 patients examined. Consequently, induced levels of CD26 cell surface expression on either normal activated and malignant B-cells coincided with the enhancement of DPP IV activity detected on the surface of these cells. Reverse transcription polymerase chain reaction analyses showed that the transcript levels of the CD26 gene was higher in normal activated B-cells and B-CLL cells than in resting B-cells, suggesting that CD26 was expressed at the level of transcriptional activation. These observations provide evidence of the abnormal expression of DPPIV/CD26 in B-CLL which, therefore, may be considered as a novel marker for B-CLL. Further investigation in relation to CD26 expression and other B malignancies needs to be defined.

HBV-specific lymphoproliferative and cytokine responses in patients with chronic hepatitis B

BACKGROUND/AIMS Hepatitis B virus specific T cell responses are crucial for viral elimination but their nature is not fully understood. METHODS We studied the regulation of proliferation and cytokine production after antigenic stimulation in peripheral blood mononuclear cells from chronically HBV-infected patients and subjects with natural immunity after recovery from an acute infection. Proliferation and production of interferon-gamma, IL-10 and tumor necrosis factor-alpha were determined after stimulation with HBcAg, HBeAg or HBsAg in the absence or presence of IL-12 or neutralizing antibodies to IL-12, interferon-gamma, IL-4, IL-10 or tumor necrosis factor-alpha. RESULTS Upon stimulation with HBcAg or HBeAg, peripheral blood mononuclear cells from chronic hepatitis B virus patients displayed a clear class-II restricted proliferative response (SI greater than 2.5). Both interferon-gamma (less than 50 IU/ml) and IL-10 levels up to 600 pg/ml were detected. Proliferative or cytokine responses to HBsAg were very weak or absent. Addition of IL-12 to HBeAg-stimulated cultures increased the production of interferon-gamma to more than 200 IU/ml in all patients and slightly increased the production of IL-10. Neutralization of IL-10 increased the HBeAg-induced interferon-gamma production but had no effect on tumor necrosis factor-alpha production. Addition of anti-IL-4 or anti-tumor necrosis factor-alpha had no significant influence on proliferation or cytokine release. Importantly, in both chronic hepatitis B virus patients and naturally immune subjects, IL-12 induced proliferative and interferon-gamma responses in peripheral blood mononuclear cells stimulated with HBsAg. CONCLUSIONS Our data indicate that peripheral blood mononuclear cells from chronic hepatitis B virus patients proliferate and produce interferon-gamma and IL-10 upon HBeAg but not upon HBsAg stimulation. IL-12 augments the HBeAg-induced responses and, additionally, provokes proliferation and interferon-gamma production in HBsAg-stimulated cultures.

Platelet [alpha]2-adrenoceptor density in humans: relationships to stress-induced anxiety, psychasthenic constitution, gender and stress-induced changes in the inflammatory response system

BACKGROUND This study examined the effects of psychological stress on platelet alpha2-adrenergic receptor (alpha2-AR) binding sites in relation to stress-induced anxiety and changes in the inflammatory response system (IRS). METHODS The maximum number of binding sites (Bmax) and their affinity (Kd) for [3H]rauwolscine, a selective alpha2-AR antagonist, and the stimulated production of tumor necrosis factor-alpha (TNFalpha), the Th1-like cytokine, interferon-gamma (IFNgamma), and the Th2-like cytokines, interleukin-10 (IL-10) and IL-5, were measured in 35 university students a few weeks before (baseline) as well as on the day before a difficult, oral examination (stress condition). The State-Trait-Anxiety Inventory (STAI) was recorded during both conditions. The Minnesota Multiphase Personality Inventory (MMPI-2) was used to assess psychasthenia (Scale 7). RESULTS Academic examination stress induced a significant increase in alpha2-AR density in students whose STAI scores increased in the stress period, in female students and in students who scored higher on psychasthenia. There were significant and positive correlations between stress-induced anxiety and changes in alpha2-AR density. Stress-induced anxiety was accompanied by a pro-inflammatory and Th1-like response, i.e. increased IFNgamma and TNFalpha production. The stress-induced changes in platelet alpha2-AR density were significantly and positively related to the production of TNFalpha, IL-10 and IL-5 and negatively to that of IFNgamma. CONCLUSIONS Subchronic psychological stress in humans induces increased alpha2-AR density, which is related to stress-induced anxiety, an anxiety-prone constitution and female sex. Increased alpha2-AR density is accompanied by a Th2-like response and increased TNFalpha production. The results suggest that: (i) alpha2-AR density is sensitive to graded differences in stress-induced anxiety; and (ii) psychological stress is accompanied by intertwined responses in the catecholaminergic system, such as alpha2-ARs, and the IRS, such as Th1/Th2-like functions and the production of TNFalpha.

Does Epidural Analgesia During Labor Alter Postpartum Maternal IL-6 Serum Levels?

Recent studies suggest that cytokines can participate in the pathophysiology of normal and abnormal pregnancy and parturition. Interleukin 6 (IL-6), an early and integral responder in the cascade of host mediators after injury, exerts multiple biological activities which comprise the induction of fever, the modulation of the synthesis of acute-phase proteins by the liver, activation of B and T lymphocytes, and the stimulation of hemopoietic progenitor and stem cells.

The Effect of Epidural Analgesia During Labor on the Immune System. Part 2. Neonatal Blood IL-6 Levels

Birth is a stressful event for the child. A lot of physiological changes happen during the early extrauterine period to make an independent existence possible. He must breathe air, change his circulatory pattern, maintain his body temperature, limit the invasion of microorganisms, ingest, digest, and assimilate food for activity and growth, provide new routes for excretion of metabolic end products, restrict the hemorrhage of trauma, and expand his hematopoietic system. In these processes, cytokines might play an important role.