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Journal Article 2011; 32(6): 774-780 PubMed PMID: 22286798 Citation  Keywords:  Adult, Affect:physiology, Autonomic Nervous System:physiology, Catecholamines:blood, Cytokines:blood, Emotions:physiology, Female, Humans, Male, Memory, Episodic, Odorants, Smell:physiology, Young Adult,.   

OBJECTIVE: The "Proust phenomenon" occurs when a certain smell evokes a specific memory. Recent studies have demonstrated that odor-evoked autobiographic memories are more emotional than those elicited by other sensory stimuli because of the direct neural communication between the olfactory system and the amygdala. The amygdala is known to regulate various physiological activities including the endocrine and immune systems; therefore, odor-evoked autobiographic memory may trigger various psychological and physiological responses; however, the responses elicited by this memory remains obscure. In this study, we aimed to investigate the psychological and physiological responses accompanying odor-evoked autobiographic memory.

METHODS: We recruited healthy male and female volunteers and investigated changes in their mood states and autonomic nervous, endocrine, and immune activities when autobiographic memory was evoked in the participants by asking them to smell an odor(s) that was nostalgic to them.

RESULTS: The autobiographic memories associated with positive emotion resulted in increased positive mood states, such as comfort and happiness, and decreased negative mood states, such as anxiety. Furthermore, heart rate was decreased, skin-conductance level was increased, and peripheral interleukin-2 level was decreased after smelling the nostalgic odor. These psychological and physiological responses were significantly correlated.

CONCLUSIONS: The present study suggests that odor-evoked autobiographic memory along with a positive feeling induce various physiological responses, including the autonomic nervous and immune activities. To the best of our knowledge, the present study is the first to observe an interaction between odor-evoked autobiographic memories and immune function....

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Comparative Study 2010; 31(5): 657-662 PubMed PMID: 21173747 Citation  Keywords:  Adult, Cells, Cultured, Cytokines:metabolism, Dental Implantation:instrumentation, Dental Implants, Female, Humans, Interferon-gamma:metabolism, Interleukin-1beta:metabolism, Interleukin-4:metabolism, Interleukin-6:metabolism, Lymphocytes:immunology, Male.   

OBJECTIVES: In most of patients in need of implantation treatment in the oral cavity, implants heal well, nevertheless, there are some individuals, in whom titanium implants fail for reasons, which remain unclear.

DESIGN: The aim of our study was to determine if there is a difference between metal influenced IL-1β, IL-4, IL-6, TNF-α and IFN-γ cytokines production in patients with successfully healed implants compared to those, whose implant therapy was unsuccessful.

SETTING: The two study groups included 12 patients with failed dental titanium implants and 9 patients with successfully healed implants. In the subjects, cytokine production was established after lymphocyte cultivation with mercury, nickel and titanium antigens.

RESULTS: IL-1β levels were significantly increased in all patients after stimulation with titanium and in patients with accepted implants compared to patients with failed implants after the stimulation with mercury and titanium. Titanium caused significantly increased IL-6 production in all patients. TNF-α and IFN-γ levels were also significantly increased after the stimulation with titanium. Significantly increased TNF-α levels were found in patients with accepted implants as compared to patients with failed implants.

CONCLUSIONS: Increased production of IL-1β a IL-6 cytokines in reaction to titanium and increased production of TNF-α and IFN-γ cytokines in reaction to mercury, which is very often present in the form of amalgam in the oral cavity of persons in need of implant therapy, can play an important role in immune reactions during implant healing process. In patients with failed titanium implants, decreased production of these cytokines may participate in implant failure....

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Journal Article 2010; 31(3): 375-383 PubMed PMID: 20588232 Citation  Keywords:  Ascites:metabolism, Cyst Fluid:metabolism, Cytokines:blood, Diagnosis, Differential, Female, Humans, Middle Aged, Ovarian Neoplasms:blood,.   

OBJECTIVE: To analyze the profiles of interleukin-2 (IL-2), IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1) and interferon-gamma (IFN-gamma) in serum and the tumor microenvironment (cyst fluid, ascites) in women with ovarian cancer or benign ovarian tumors to find the differences in their immunological status. We also estimated serum cytokines as biomarkers to distinguish preoperatively between malignant or benign character of tumors.

DESIGN: Prospective study.

SETTING: Tertiary referral hospital.

POPULATION: 51 women with epithelial ovarian cancer, 26 with benign ovarian tumors of epithelial origin and 21 healthy controls.

METHODS: The levels of cytokines were measured using ELISA sets.

RESULTS: We did not found differences in the levels of IFN-gamma, TNF-alpha and IL-2 in all fluids isolated from patients with malignant or benign tumors. Women with advanced cancer had significantly higher serum IL-6, IL-10 and TGF-beta1 levels than women with early stages or benign tumors. Moreover, women with very advanced cancer in whom the optimal cytoreduction was disabled had the highest serum levels of IL-10, TGF-beta1 and IL-8. The concentrations of IL-6 and IL-8 were higher in ascites of cancer patients than in ascites of women with benign tumors. The areas under curves constructed for the selected cutoff serum cytokines levels (AUC-ROC) showed good predictive values for IL-6 (0.87), IL-10 (0.836) and IL-8 (0.797).

CONCLUSIONS: Our results indicate on intensified inflammatory process in women with ovarian cancer (accompanied by their immunosuppression). Preoperative analysis of serum IL-6, IL-10 and IL-8 may improve the differential diagnosis of ovarian tumors....

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Journal Article 2008; 29(3): 303-311 PubMed PMID: 18580842 Citation  Keywords:  Adult, Amniotic Fluid:physiology, Bayes Theorem, Biomarkers, Cesarean Section, Cytokines:blood, Delivery, Obstetric, Female, Fetal Blood:chemistry, Humans, Infant, Newborn, Intercellular Adhesion Molecule-1:blood, Interleukin-6:blood, Interleukin-8:blood,.   

BACKGROUND: Intraamniotic infections negatively affect the mortality and morbidity in parturients and newborns. The prognosis of the disease is associated with a timely diagnosis of these conditions. One of approaches to providing timely information on the risk of the initiation of intra-amniotic infection and early-onset neonatal sepsis is the examination of cytokine levels.

OBJECTIVES: The purpose of the work was to evaluate the importance of the cytokines, IL-6, IL-8, and TNF-alpha, and the adhesive molecule, sICAM-1, as risk factors for early-onset neonatal sepsis and intra-amniotic infections.

METHODS: In a group of 152 women we sampled the blood from the umbilical cord vein immediately after delivery for the determination of the cytokines IL-6, IL-8 and TNF-alpha, and the adhesive molecule, sICAM-1, in newborns.

RESULTS: The sensitivity and specificity results are as follows, respectively: IL-6, 0.800 and 0.972; TNF-alpha, 0.364 and 0.943; IL-8, 0.875 and 0.965; and sICAM-1, 0.833 and 0.952.

CONCLUSIONS: For screening purposes, it is suitable to determine levels of IL-8, IL-6, and sICAM-1. For the screening examination, one of the cytokines mentioned is sufficient, i.e., IL-8 or IL-6, or the level of the adhesive molecule, sICAM-1. It is unnecessary to combine these markers....

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Journal Article 2008; 29(3): 287-291 PubMed PMID: 18580840 Citation  Keywords:  Animals, Anti-Inflammatory Agents:pharmacology, Antidepressive Agents:pharmacology, Biomarkers, Brain Chemistry:drug effects, Cytokines:physiology, Depression:drug therapy, Humans, Inflammation:drug therapy, Intestinal Absorption:physiology, Intestinal Mu.   

: This paper hypothesizes that inflammatory, oxidative and nitrosative (IO&NS) pathways, and an increased translocation of LPS from gram-negative bacteria are causally related to depression following external (psychological) and internal (organic) stressors and that IO&NS pathways are novel targets for antidepressant development. We review that depression is accompanied by an inflammatory reaction as indicated by an increased production of pro-inflammatory cytokines, such as interleukin-1beta (IL-1beta), IL-6, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN)-gamma. These cytokines are stress-sensitive and may cause depressive behaviors. The latter may be induced by an increased catabolism of tryptophan, the precursor of serotonin, to neurotoxic TRYCATs (tryptophan catabolites along the indoleamine oxidase pathway). Inflammatory biomarkers are detected in animal models of depression. Newly developed animal models of depression are based on induced inflammation. Most if not all antidepressants have specific anti-inflammatory effects. Anti-inflammatory compounds may augment the clinical efficacy of antidepressants. Depression is also accompanied by an IgM-related (auto)immune response directed against disrupted lipid membrane components, such as phosphatidyl-inositol, by-products of lipid peroxidation, e.g. azelaic acid and malondialdehyde, and NO-modified amino-acids, which are normally not detected by the immune system but due to damage caused by O&NS have become immunogenic. Increased translocation of lipopolysaccharide from gram-negative bacteria, which may be induced by internal and external stressors, may further aggravate the induced IO&NS pathways....

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Comparative Study 2008; 29(2): 205-221 PubMed PMID: 18404134 Citation  Keywords:  Adult, Cytokines:blood, Enterococcus faecalis:isolation & purification, Female, Fetal Membranes, Premature Rupture:blood, Humans, Infant, Newborn, Lactobacillus:isolation & purification, Pregnancy, Pregnancy Complications, Infectious:blood, Risk Factors, .   

BACKGROUND: Infections are among the most frequent causes of premature delivery and premature discharges of amniotic fluid. The vaginal ecosystem significantly contributes to the development of these conditions. Premature rupture of membranes (PROM) and preterm premature rupture of membranes (pPROM) are associated with an increased risk of intra-amniotic infection. The intra-amniotic infection negatively affects perinatal morbidity and mortality of newborns.

OBJECTIVES: Finding of relationship of vaginal microflora to PROM, pPROM and the risk of early-onset neonatal sepsis.

METHODS: A prospective study was implemented in 152 women with singleton gestations with PROM (n=52) and pPROM (n=47); the control group included 53 women with physiologic pregnancy and delivery at normal term without PROM. In all the women, aerobic cultivations from the vagina and cervix for Chlamydia trachomatis were provided before initiation of antibiotic treatment, the microbial picture of vagina was examined, and the cultivation examination of urine was carried out. The placenta was subjected to histopathologic examination. For the diagnosis of early-onset sepsis, we used concentrations of cytokines IL-6, IL-8, TNF-alpha, and the adhesion molecule, ICAM-1, from the venous umbilical blood taken immediately after delivery and cutting of the umbilical cord. Demonstrated early neonatal sepsis served as a further criterion.

RESULTS: The most frequent bacteriologic findings throughout the group were coagulase-negative Staphylococci, Ureaplasma, Candida albicans, and Streptococcus viridans. Women with a diagnosis of urinary tract infection or diabetes mellitus were excluded from the study. We found no statistically significant relationship between a specific bacterial strain and PROM and pPROM. We found a statistically significant association between the risk for intra-amniotic infection and the finding of S. viridans (p<0.001). There was also a statistically significant relationship between the microbiologic picture of the vagina VI and infection risk (p<0.002).

CONCLUSIONS: Based on results of the present study, it is clear that the use of cultivation and microscopic findings in the vagina and cervix for the timely diagnosis of the risk of early-onset neonatal sepsis is restricted....

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Journal Article 2007; 28(6): 826-831 PubMed PMID: 18063923 Citation  Keywords:  Adult, Anti-Inflammatory Agents:immunology, Cytokines:immunology, Depressive Disorder:metabolism, Female, Gene Expression Regulation:immunology, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase:immunology, Inflammation:metabolism, Interferon-gamma:immunology,.   

: Immune activation is accompanied by induction of indoleamine (2,3)-dioxygenase (IDO), an enzyme which degrades tryptophan, a phenomenon which plays a role in the pathophysiology of major depression and post-natal depression and anxiety states. TRYCATs - tryptophan catabolites along the IDO pathway - such as kynurenine, kynurenic acid, xanthurenic acid, and quinolinic acid, have multiple effects, e.g. apoptotic, anti- versus pro-oxidant, neurotoxic versus neuroprotective, and anxiolytic versus anxiogenic effects. The aim of the present study was to study the immune effects of the above TRYCATS. Toward this end we examined the effects of the above TRYCATs on the LPS + PHA-induced production of interferon-gamma (IFNgamma), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNFalpha) in 18 normal volunteers. We found that the production of IFNgamma was significantly decreased by all 4 catabolites. Xanthurenic acid and quinolinic acid decreased the production of IL-10. Kynurenine, kynurenic acid, and xanthurenic acid, decreased the IFNgamma/IL-10 production ratio, whereas quinolinic acid increased this ratio. Kynurenic acid significantly reduced the stimulated production of TNFalpha. It is concluded that kynurenine, kynurenic acid, and xanthurenic acid have anti-inflammatory effects trough a reduction of IFNgamma, whereas quinolinic acid has pro-inflammatory effects in particular via significant decreases in IL-10. Following inflammation-induced IDO activation, some TRYCATs, i.e. kynurenine, kynurenic acid, and xanthurenic acid, exert a negative feedback control over IFNgamma production thus downregulating the initial inflammation, whereas an excess of quinolinic acid further aggravates the initial inflammation....

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Comparative Study 2007; 28(6): 875-880 PubMed PMID: 18063921 Citation  Keywords:  Adult, Analysis of Variance, Arachidonic Acid:administration & dosage, Cytokines:immunology, Depression:drug therapy, Docosahexaenoic Acids:administration & dosage, Dose-Response Relationship, Drug, Eicosapentaenoic Acid:administration & dosage, Female, H.   

BACKGROUND: We have shown that a depletion of omega3 polysaturated fatty acids (PUFAs) plays a role in the pathophysiology of depression, in part because omega3 PUFAs have anti-inflammatory effects. omega3 PUFAs are frequently employed to treat depression. Most if not all antidepressants have negative immunoregulatory effects by decreasing the production of proinflammatory cytokines, such as interferon-gamma (IFNgamma) and/or increasing that of anti-inflammatory cytokines, such as interleukin10 (IL-10).

AIM: The aim of the present study was to examine the immunoregulary effects of the omega3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and the omega6 PUFA, arachidonic acid (AA), on the production of interferon-gamma (IFNgamma), interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNFalpha).

METHODS: This study examines the ex vivo effects of EPA (4.5 microM, 9 microM, 18 microM and 45 microM), DHA (1.3 microM, 3 microM, 6 microM and 13 microM) and AA (8 microM, 16 microM, 32 microM and 80 microM) on the LPS + PHA-stimulated production of IFNgamma, IL-10 and TNFalpha, and on the IFNgamma/IL-10 production ratio.

RESULTS: We found that EPA did not have any significant effects on the above cytokines. DHA significantly increased the IFNgamma/IL-10 production ratio, caused by a greater reduction in IL-10 than in IFNgamma. AA significantly decreased TNFalpha production.

DISCUSSION: The results show that DHA induces a Th-1-like immune response and that AA has anti-inflammatory effects by decreasing the production of TNFalpha. Thus, the immune effects of omega3 PUFAs are not compatible with what is expected from antidepressive substances. The results of the present study show that treatment with fish oils, containing DHA, should be avoided in the treatment of depression. Toward this end, highly concentrated and pure EPA seems to be indicated....

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