Time has come to include Human Papillomavirus (HPV) testing in sperm donor banks.

HPV is well known as a potential cause of cervical cancer. Less well known is its link to temporal subfertility that is caused by binding of infectious virions to the spermatozoa's head which induces sperm-DNA damage and causes a reduction in clinical pregnancy rates in women receiving HPV positive semen. This impact on the global fertility burden remains greatly underestimated and underexplored. This risk of reduced fertility due to infectious HPV in sperm is especially important when donor sperm insemination is considered, since testing for the presence of HPV virions before use seems warranted. We tested 514 donor sperm samples from 3 different sperm banks for 18 different HPV types. Overall 3.9% (20/514) of tested donor sperm was positive for HPV, with different prevalence among the 3 different sperm banks (3.6% bank A, 3.1% bank B and 16.7% bank C). Also the HPV virion per spermatozoon ratio in donor samples was similar across the different sperm banks (95% CI 0,01 to 1,07 HPV virions/spermatozoon). When HPV positive donor sperm was used, no clinical pregnancies resulted, whereas when HPV negative donor sperm was used the clinical pregnancy rate was 14.6%. From both a cost/benefit and a safety point of view we recommend that donor sperm should always be tested for HPV before using it for insemination.

Morphometrical analysis of preantral follicular survival of VEGF-treated bovine ovarian cortex tissue following xenotransplantation in an immune deficient mouse model.

The increasing number of cancer survivors the past decades, has sparked the need for fertility preservation strategies. Due to predominantly ethical constraints, human research material is scarce. A bovine in vitro model is a valuable alternative. Therefore, the following objectives were defined: 1) to xeno-graft bovine ovarian cortex tissue in immune deficient mice as a study-model for female fertility preservation strategies; 2) to stereologically quantify vascularization in Vascular Endothelial Growth Factor (VEGF)-treated and non-treated tissue; 3) to study preantral follicular survival in situ, after xenotransplantation. Bovine ovarian tissue strips were incubated with or without VEGF prior to grafting into female, neutered BALB/c-nu mice (n=16). Non-transplanted cortical tissue was used as a control. At time zero (control), two (2 weeks) and four (4 weeks) weeks after transplantation, grafts were retrieved and assessed by von Willebrand Factor and caspase-3 immunostaining. Data were analyzed using a linear mixed model. In the VEGF+ grafts, 31% of the follicles were considered 'alive' 2 weeks after transplantation, compared to only 17% in the VEGF- grafts (P<0.05). However, no difference could be detected 4 weeks after transplantation (P=0.76) with less follicles being considered 'alive' after transplantation (22%), compared to the control (47.5%) (P<0.05). Finally, the vascular surface density was significantly less in the grafts, irrespective of the transplantation period or the use of VEGF. Although the transplantation process overall negatively influenced the number of viable follicles and vascular density, VEGF exposure prior to transplantation can favor follicle survival during a 2 weeks transplantation period.

Human Papillomavirus (HPV) virion induced cancer and subfertility, two sides of the same coin.

In the natural history of HPV infections, the HPV virions can induce two different pathways, namely the infec- tious virion producing pathway and the clonal transforming pathway. An overview is given of the burden that is associated with HPV infections that can both lead to cervical cancer and/or temporal subfertility. That HPV infections cause serious global health burden due to HPV-associated cancers is common knowledge, but that it is also responsible for a substantial part of idiopathic subfertility is greatly underestimated. The bulk of the detected HPV DNA whether in men or women is however infectious from origin. Because the dissociation between HPV viruses and HPV virions or infection and disease remains difficult for clinicians as well as for HPV detection, we propose a review of the different effects caused by the two different HPV virion induced pathways, and highlight the mechanisms that are responsible for causing transient subfertility and cancer.

In depression, bacterial translocation may drive inflammatory responses, oxidative and nitrosative stress (O&NS), and autoimmune responses directed against O&NS-damaged neoepitopes.

OBJECTIVE: Depression is accompanied by activation of immuno-inflammatory and oxidative and nitrosative stress (IO&NS) pathways, and increased IgM/IgA responses to lipopolysaccharide (LPS) of gram-negative commensal bacteria. The latter suggests that bacterial translocation has caused IgM/IgA responses directed against LPS. Bacterial translocation may drive IO&NS responses. METHOD: To examine the associations between IgM/IgA responses to LPS and IO&NS measurements, including plasma/serum interleukin-1 (IL-1), tumor necrosis factor (TNF)α, neopterin, lysozyme, oxidized LDL (oxLDL) antibodies, peroxides, and IgM (auto)immune responses against malondialdehyde (MDA), azelaic acid, phophatidyl inositol (Pi), NO-tryptophan and NO-tyrosine in depressed patients and controls. RESULTS: We found significant positive associations between IgM/IgA responses to LPS and oxLDL antibodies, IgM responses against MDA, azelaic acid, Pi, NO-tryptophan, and NO-tyrosine. The IgA responses to LPS were correlated with lysozyme. There were no significant positive correlations between the IgM/IgA responses to LPS and IL-1 and neopterin. CONCLUSION: The findings show that in depression there is an association between increased bacterial translocation and lysozyme production, an antibacterial compound, O&NS processes, and autoimmune responses directed against O&NS generated neoantigenic determinants. It is suggested that bacterial translocation may drive IO&NS pathways in depression and thus play a role in its pathophysiology.

Unravelling the needs of singly in vitro-produced bovine embryos: from cumulus cell co-culture to semi-defined, oil-free culture conditions.

Producing bovine in vitro embryos individually is a challenge as it generally leads to impaired embryo development. Earlier research optimised a single embryo in vitro production (IVP) protocol using serum, cumulus cells and oil during culture. As some of these factors are undesirable in certain circumstances, the present study investigated their necessity and possible interactions, and defined their role during single-embryo culture. Although the cumulus cell monolayer produced progesterone, it appeared not to be a key factor in supporting single-embryo development. Because in vitro culture in large medium volumes was shown to impair single-embryo development, two new oil-free culture protocols were tested. Using a 30-µL droplet of medium in 96-well plates with a small surface area resulted in comparable blastocyst rates to those obtained under oil. When serum was used, co-culture with cumulus cells seems necessary, leading to consistently high blastocyst rates. Finally, a serum-free, oil-free culture system using insulin, transferrin, selenium and BSA resulted in embryos with similar total cell numbers and apoptotic cell ratios, but blastocyst rates did not equal those obtained with serum and co-culture. This research additionally stresses the fact that specific interaction mechanisms between somatic cells and a developing in vitro embryo are far from unravelled.

Correlation between male age, WHO sperm parameters, DNA fragmentation, chromatin packaging and outcome in assisted reproduction technology.

In the human, male ageing results in reproductive hormonal and cellular changes that can influence semen quality (volume, motility, concentration and morphology) and ultimately result in a reduced fertilising capacity and a longer 'time to pregnancy' for ageing men as well as an increased risk for miscarriage. This prospective cohort study of 278 patients undergoing a first in vitro fertilisation or intracytoplasmic sperm injection treatment was undertaken to examine whether patient's age was reflected in sperm motility, concentration, morphology as well as in DNA fragmentation (DFI) and immature chromatin (unprocessed nuclear proteins and/or poorly condensed chromatin) as measured by the sperm chromatin structure assay. This study also investigated the possible influence of male age (after correcting for female age) on their fertilising capacity, on obtaining a pregnancy and a healthy baby at home. Logistic regression analysis did not reveal any male age-related influences on sperm parameters like concentration, motility or morphology. No significant male age-related increase in DFI or immature chromatin was demonstrable for these patients. Elevated male age, after correcting for female age, was not related to lower fertilisation rates or significant decreases in the chance for a healthy baby at home.

In search for the general population's semen profile: the study of sperm parameters in partners of women with chronic anovulation.

BACKGROUND: Human fertility is linked to sperm quality and therefore the establishment of reference values for normality is mandatory. AIMS: The first aim was to establish a reference profile of men in the general population by examining the semen of partners of women with chronic anovulation. The second aim was to determine the prevalence of sperm abnormalities in this patient group. METHODS: Sperm samples of 304 partners of patients with chronic anovulation were analysed prospectively. Semen samples were examined according to WHO guidelines, for sperm morphology Tygerberg strict criteria were used. We compared the results of this study with the cut-off values for normality we obtained in a previous study performed in our centre. RESULTS: The mean value was 3.1 ml for volume, 64.7 mill / ml for concentration, 51.9% for progressive motility (grade a + b motility) and 7.4% for sperm morphology. Single parameter and double parameter abnormalities were observed in 42.7% and 8.2% of cases respectively. A normal sperm sample for all three parameters was noted in 46% of cases. Oligo-Astheno-Teratozoospermia was present in 3.0% of cases while azoospermia was found in two patients (0.7%). CONCLUSION: We believe that the study of sperm parameters in partners of patients with chronic anovulation can be used to study the prevalence of sperm abnormalities in the general population. Our data show that semen abnormalities are not uncommon in partners of women with chronic anovulation, highlighting the importance of a semen examination in every infertility work-up, even in case of obvious female pathology.

[The Hypo Ionic Protein Profile (HIPP). Laboratory analytical evaluation in Complementary and Alternative Medicine]. / Het hypo-ionische eiwitprofiel. Evaluatie van een laboratoriumanalyse uit de complementaire en alternatieve geneeskunde.

The hypo ionic protein profile (HIPP) is a test based on the reticulo-endothelial index of Sandor. We evaluated the analytical performance of this test by comparing the obtained data in the HIPP to the concentration of some frequently measured specific serum proteins. The alfa euglobulin zone mainly comprises of ceruloplasmin, complement factor 3, apolipoprotein B and haptoglobin. The beta and gamma euglobulin zone reflect the concentration of the immunoglobulins. Since these proteins cannot be distinguished from each other, the diagnostic value of the HIPP will be limited. The HIPP is an outdated and aspecific assay for protein measurements.

Combination of serum markers related to several mechanisms in Alzheimer's disease.

Alzheimer's disease (AD) probably involves several pathobiochemical mechanisms and this may be reflected by changes in different serum components. The present study investigated whether the combined analysis of serum molecules related to different mechanisms improves the discrimination of AD patients from healthy controls. Serum of patients with AD was analyzed for a broad spectrum of marker molecules, including 11 inflammatory proteins, 12 sterol intermediates and phytosterols, 2 brain-specific proteins and 4 constituents involved in homocysteine homeostasis. The serum molecule concentrations were combined in a logistic regression model, using a forward stepwise inclusion mode. The results showed that the combination of interleukin-6 (IL-6) receptor, protein alpha1 fraction, cysteine and cholesterol concentrations improved the discrimination between AD patients and healthy controls compared to the single markers. In conclusion, the results of this study have shown that the complex pathology in AD is reflected in a pattern of altered serum concentrations of several marker molecules related to several pathobiochemical mechanisms.

[Serum markers in relation to cognitive functioning in an aging population: results of the Maastricht Aging Study (MAAS)]. / Serummarkers in relatie tot cognitieve functies bij ouderen. Resultaten van de Maastricht Aging Study (MAAS).

Little is known of the biochemical processes of cognitive decline during 'healthy' aging. Biological markers in body fluids, such as blood, could provide insight in those processes. In the present studies serum concentrations of different markers have been correlated to cognitive functioning of cognitively healthy aging individuals over a period of six years (mean age 57 years, SD 11, n = 93). Markers were related to mechanisms known to be involved in Alzheimer's disease, including inflammation, cholesterol homeostasis and homocysteine homeostasis. Domains of cognitive function addressed were cognitive speed (Letter-Digit Coding test), attention and information processing (Stroop test), and memory (Word Learning test: Total Words and Delayed Recall). Baseline concentrations of haptoglobine, homocysteine, lathosterol and lanosterol were negatively correlated with cognitive functioning on the Stroop test over the whole follow-up period of six years. Concentrations of all markers, i.e. haptoglobine, C-reactive protein, homocysteine, lathosterol and lanosterol, were also negatively correlated with functioning on the Word Learning test (Delayed Recall and for some markers also with the Total Words) over the whole six-years follow-up period. In conclusion, concentrations of serum markers related to inflammation, homocysteine and cholesterol homeostasis are not only associated with Alzheimer's disease, but also with cognitive functioning in the cognitively healthy aging population.

Inflammation markers in relation to cognition in a healthy aging population.

The relation between serum inflammatory protein levels and cognitive performance was investigated in a healthy population. Individuals were tested during 6 years of follow-up. Serum concentrations of 10 inflammatory proteins were correlated to cognitive speed (Letter-Digit Coding Test, LDCT), attention and information processing (Stroop) and memory (Word Learning). Haptoglobin levels at baseline correlated negatively with cognitive performance on the Stroop and Word Learning Recall test over the 6 years follow-up period. C-reactive protein (CRP) levels at baseline correlated negatively with performance on the Word Learning tests over the 6 years follow-up period. Thus, relatively high concentrations of haptoglobin and C-reactive protein may be indicative for impaired cognitive performance.

Increased serum albumin, gamma globulin, immunoglobulin IgG, and IgG2 and IgG4 in autism.

BACKGROUND: Research on the biological pathophysiology of autism has found some evidence that immune alterations may play a role in the pathophysiology of that illness. As a consequence we expected to find that autism is accompanied by abnormalities in the pattern obtained in serum protein electrophoresis and in the serum immunoglobulin (Ig) and IgG subclass profile. METHOD: We examined whether subjects with autism showed changes in total serum protein (TSP) and the serum concentrations of albumin, alpha1 globulin, alpha2 globulin, beta globulin and gamma globulins, IgA, IgM and IgG and the IgG subclasses IgG 1, IgG2, IgG3 and IgG4, compared with normal controls. RESULTS: We found significantly increased concentrations of TSP in autistic subjects, which were attributable to increased serum concentrations of albumin and gamma globulin. Serum IgG, IgG2 and IgG4 were also significantly raised. In autism there were significant and positive correlations between social problems and TSP and serum gamma globulin and between withdrawal symptoms and TSP and serum albumin and IgG. CONCLUSIONS: The results suggest that autism is characterized by increased TSP, a unique pattern obtained in serum protein electrophoresis, i.e. increased serum albumin and IgG, and by a specific IgG subclass profile, i.e. increased serum IgG2 and IgG4. The increased serum concentrations of IgGs in autism may point towards an underlying autoimmune disorder and/or an enhanced susceptibility to infections resulting in chronic viral infections, whereas the IgG subclass skewing may reflect different cytokine-dependent influences on autoimmune B cells and their products.

Interleukin (IL)-6, IL-8 and IL-10 in serum and CSF of Trypanosoma brucei gambiense sleeping sickness patients before and after treatment.

Serum and cerebrospinal fluid (CSF) concentrations of interleukin (IL)-6, IL-8, IL-10, tumour necrosis factor-alpha and interferon-gamma were determined in 46 Trypanosoma brucei gambiense sleeping sickness patients in DR Congo, before and after treatment. According to their CSF cell number before treatment, patients were classified as early-stage (0-5 cells/microL), intermediate-stage (6-20 cells/microL) or late-stage patients (> 20 cells/microL). In serum, slightly higher IL-8 concentrations were found in early-stage patients compared to intermediate- or late-stage patients. These high IL-8 levels dropped after treatment. Higher IL-10 concentrations were detected in serum of patients in intermediate or late stage compared to early-stage patients. In both intermediate- and late-stage groups, serum IL-10 decreased after treatment. In CSF, elevated concentrations of IL-6, IL-8 and especially of IL-10 were observed in late-stage T. b. gambiense patients. After treatment, these concentrations dropped to levels similar to those of the other patients. Tumour necrosis factor-alpha was detected only in a few serum and CSF samples, which were scattered over the different patient groups. Interferon-gamma was detected in serum of 5 patients and remained undetectable in CSF.

Platelet alpha2-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.

Immunotherapy with interferon-alpha in patients affected by chronic hepatitis C induces an intercorrelated stimulation of the cytokine network and an increase in depressive and anxiety symptoms.

Immunotherapy with interferon-alpha (IFNalpha) may induce depressive symptoms, anxiety and major depression when administered for at least 1-3 months at a dose of 3-10 MUI daily, twice or three times a week. Previously, it has been shown that immunotherapy with interleukin-2 (IL-2) significantly induces the cytokine network, as measured by increases in serum IL-6, IL-10 and the IL-2 receptor (IL-2R), and that the immunotherapy-induced changes in the cytokine network are significantly correlated with the increases in depression ratings. The main aim of this study was to examine the effects of immunotherapy with IFNalpha on the cytokine network in relation to changes in depression and anxiety ratings. Fourteen patients, affected by chronic active C-hepatitis, were treated with IFNalpha (3-6 MUI s.c. three/six times a week for 6 months) and had measurements of serum IFN-gamma (IFNgamma), IL-2, IL-6, IL-6R, IL-8 and IL-10 before starting therapy and 2, 4, 16 and 24 weeks after immunotherapy with IFNalpha. Severity of depression and anxiety were measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A), respectively. Repeated measure (RM) design ANOVAs showed significantly higher MADRS and HAM-A scores 2-4 weeks and 4-6 months after starting IFNalpha-based immunotherapy than at baseline. RM design ANOVAs showed significantly higher serum IL-6 and IL-8 levels 2-4 weeks after starting IFNalpha-based immunotherapy and higher serum IL-10 levels 2-4 weeks and 4-6 months after starting therapy than at baseline. There were significant relationships between the IFNalpha-induced changes in serum IL-6 or IL-8 and the depression and anxiety scores. The findings show that IFNalpha-based immunotherapy induces the cytokine network and that IFNalpha-induced increases in IL-6 predicts the development of depressive symptoms. Depressive symptoms following IFNalpha treatment may be secondary to cytokine induction, including that of IL-6.

Association between immune activation and early depressive symptoms in cancer patients treated with interleukin-2-based therapy.

The relationship between immune activation and the development of early depressive symptoms were studied in 33 cancer patients undergoing cytokine therapy. Patients were treated either with subcutaneous IL-2 administered alone (n=13) or in association with IFN-alpha (n=5), or with IFN-alpha alone administered subcutaneously at low doses (n=5) or intravenously at high doses (n=10). The intensity of depressive symptoms was assessed during a clinical interview carried out before the start of cytokine therapy and five days later using the Montgomery and Asberg Depression Rating Scale (MADRS). On the same days, blood samples were collected for each patient to measure serum concentrations of cytokines (IL-6, IL-10, IL-1ra) and cytokine-receptors (sIL-2R, LIF-R). Results showed that patients treated with IL-2 or IL-2+IFN-alpha displayed concomitant mood symptoms and increased serum cytokine levels during treatment. In these patients, the intensity of depressive symptoms at endpoint was positively correlated with the increases measured in serum levels of IL-10 between baseline and endpoint. IL-10 is an anti-inflammatory cytokine that is produced in response to the production of pro-inflammatory cytokines, and thereby reflects an inflammatory response. These results support the hypothesis of close relationship between depressive symptoms and the activation of the cytokine network.

Insertion or deletion of the Cheo box modifies radiation inducibility of Clostridium promoters.

Radiation-inducible promoters are being used in many viral vector systems to obtain spatial and temporal control of gene expression. It was previously proven that radiation-induced gene expression can also be obtained in a bacterial vector system using anaerobic apathogenic clostridia. The effect of radiation inducibility was detected using mouse tumor necrosis factor alpha (mTNF-alpha) as a model protein under regulation of the radiation-inducible recA promoter. In this report, experiments are described in which this recA promoter was modified in order to increase radiation responsiveness. Incorporation of an extra Cheo box in the recA promoter region resulted in an increase in mTNF-alpha secretion from 44% for the wild-type promoter to 412% for the promoter with an extra Cheo box after a single irradiation dose of 2 Gy. Deletion of the Cheo box in the promoter region eliminated radiation inducibility. These results prove that the Cheo box in the recA promoter is indeed the radiation-responsive element. We also tested whether we could induce the constitutive endo-beta-1,4-glucanase promoter (eglA) via ionizing irradiation by introducing a Cheo box in the promoter region. While the use of the constitutive promoter did not lead to an increase in mTNF-alpha secretion after irradiation, the introduction of a Cheo box resulted in a 242% increase in mTNF-alpha secretion. Reverse transcriptase PCR of RNA samples isolated from irradiated and nonirradiated bacterial cultures demonstrated that the increase in secretion was the result of enhanced transcription of the mTNF-alpha gene.

Radio-responsive recA promoter significantly increases TNFalpha production in recombinant clostridia after 2 Gy irradiation.

One of the major problems with gene therapy today is the lack of tumour specificity. The use of anaerobic apathogenic clostridia as a gene transfer system can target anoxic areas within the tumour. These bacteria can be genetically modified to express therapeutic proteins such as TNFalpha locally in the tumour. As shown in our results, ionising irradiation can be used in clostridia to activate genes encoding cytotoxic agents under control of a radiation-inducible promoter. A 44% significant increase (P < 0.05) in TNFalpha secretion was seen 3.5 h after a single dose of 2 Gy. A second dose of 2 Gy was also capable of repeating gene activation and gave a significant increase of TNFalpha production of 42% (P < 0.05). These results provide evidence that spatial and temporal control of gene expression can be achieved using a radio-inducible promoter. Repetitive gene activation was feasible with a second dose of 2 Gy, indicating that fractionated radiotherapy could lead to repeated gene induction resulting in prolonged and enhanced protein expression. Gene targeting by ionising radiation could thus provide a new means of increasing the therapeutic ratio in cancer treatment.

Effects of pregnancy and delivery on the availability of plasma tryptophan to the brain: relationships to delivery-induced immune activation and early post-partum anxiety and depression.

BACKGROUND: There is now evidence that the availability of plasma tryptophan is decreased during pregnancy and the puerperium and also in patients with major depression and inflammation. The aims of the present study were to examine: (i) the effects of pregnancy and delivery on plasma tryptophan and the amino acids known to compete for the same cerebral uptake mechanism (CAAs), valine, leucine, tyrosine, phenylalanine and isoleucine; (ii) the relationships between the availability of plasma tryptophan and postpartum depression or anxiety; and (iii) the relationships between the availability of plasma tryptophan to the brain and inflammatory markers, such as serum interleukin-6 (IL-6), interleukin-1 receptor-antagonist (IL-1RA) and the leukaemia inhibitory factor receptor (LIF-R). METHODS: The above variables were measured in 13 healthy non-pregnant and in 98 pregnant women 3 to 6 days before delivery and 1 and 3 days after delivery. On each occasion the parturient women completed the state version of Spielberger State-Trait Anxiety Inventory (STAI) and the Zung Depression Rating Scale (ZDS). RESULTS: Plasma tryptophan and the tryptophan/CAA ratio were significantly lower at the end of term and after delivery than in the plasma of non-pregnant, healthy women. The tryptophan/CAA ratio was significantly lower in the early puerperium than at the end of term. There were no significant relationships between the availability of plasma tryptophan and either post-partum depression or changes in the STAI or ZDS scores in the early puerperium. The changes in the tryptophan/CAA ratio from the end of term to the early puerperium were significantly and inversely related to serum IL-6, IL-IRA and LIF-R. CONCLUSIONS: The results show that the reduction in the availability of plasma tryptophan from the end of term to the early puerperium is related to immune activation; and that the lowered availability of plasma tryptophan is not related either to depressive or anxiety symptoms in the early puerperium or to post-partum depression ensuing some months later.

Increased serum tumor necrosis factor alpha concentrations in major depression and multiple sclerosis.

There is now evidence that major depression is accompanied by activation of the inflammatory response system (IRS) as indicated by an increased production of pro-inflammatory cytokines. There is circumstantial evidence implicating pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNFalpha) in the pathogenesis of multiple sclerosis (MS). The aims of the present study were to examine (i) the serum concentrations of interleukin-6 (IL-6), IL-8, TNFalpha, IL-2 receptor (IL-2R) and CC16 (uteroglobulin), an endogenous anti-cytokine, in depressed and MS patients compared to normal controls, and (ii) the effects of treatment with antidepressants on the above IRS variables in depressed patients. Serum TNFalpha was significantly higher in depressed and MS patients than in normal controls. Serum IL-8 was significantly higher in depressed patients than in patients with MS. Serum CC16 was significantly higher in patients with MS than in normal controls and depressed patients. Nonresponders to treatment with antidepressants had significantly higher serum IL-2R and lower serum CC16 concentrations than responders to treatment. The results show that (i) depression is accompanied by activation of the IRS and that this activation is more pronounced in depression than in MS, and (ii) IRS activation in depressed patients is related to a nonresponse to treatment with antidepressants.