Priscila Vianna

Distress conditions during pregnancy may lead to pre-eclampsia by increasing cortisol levels and altering lymphocyte sensitivity to glucocorticoids

Psychological stress may affect up to 18% of all pregnant women, altering the function of both neuroendocrine and immune systems. Distress conditions may directly change the hypothalamic-pituitary-adrenal (HPA) axis, leading to increased cortisol levels and associated changes in cellular immunity. Psychological events such as high stress levels, anxiety or depression may directly or indirectly affect pregnancy and may thus lead to pre-eclampsia (PE). Here, we suggest that distress conditions during pregnancy may lead the development of PE by enhancing in vivo cortisol levels. High cortisol levels are associated with hypertension and endothelial dysfunction, features often observed in patients with PE. Lymphocytes from patients with high cortisol levels may have a reduced sensitivity to the synthetic glucocorticoid dexamethasone (DEX). Stress-related steroid resistance may disrupt the HPA axis, leading to post-natal detrimental effects such as increased allostatic load, increased pro-inflammatory cytokine levels and even depression in the offspring.

Acupuncture is effective to attenuate stress and stimulate lymphocyte proliferation in the elderly.

Acupuncture has increasingly been used to treat many conditions, including psychiatric disorders and immunological-related disorders. However, the effects of acupuncture as stress management and immune functions in the elderly are largely unclear. Here we investigated the effects of acupuncture on stress-related psychological symptoms and cellular immunity in young adults and elderly subjects. The acupuncture treatment consisted of six sessions and the procedures included the insertion of needles at bilateral acupoints LI4, SP6 and ST36. Psychological variables (depression, anxiety and stress) were investigated by means of self-assessment inventories. Peripheral blood mononuclear cells were isolated and cultured in vitro to measure mitogen-induced T-cell proliferation as well as cellular sensitivity to dexamethasone. All data were assessed before and after the intervention. Acupuncture was able to significantly reduce depression (p<0.001), anxiety (p<0.001) and stress (p<0.001) scores. The intervention also increased T-cell proliferation, with greater intensity in the elderly group (p=0.004). No changes in cellular sensitivity to dexamethasone were observed following acupuncture. We conclude that acupuncture was efficient to attenuate the psychological distress as well as to increase an important feature of cellular immunosenescence.

Peripheral toxicity in crack cocaine use disorders

A growing body of evidence suggests that crack cocaine misuse has widespread systemic and cognitive consequences, but little attention has been given to its systemic pathophysiology. We report here changes in inflammation markers, oxidative damage and brain derived neurotrophic factor in a sample of outpatients with crack cocaine use disorders. Fifty-three outpatients were recruited for this cross-sectional study and matched with fifty control subjects. The focus of this report is in between group differences in cytokines, oxidative damage and brain-derived neurotrophic factor (BDNF). Crack cocaine use was associated with higher BDNF levels when compared to controls, present only in those who used crack cocaine in the last month. Patients also had higher circulating levels of IL-1β, TNF-α and IL-10 when compared to controls. There were no significant differences in oxidative damage between patients and controls. These results represent a first demonstration that crack cocaine use disorders entail an activation of the reward, immune and inflammatory systems.

Effect of nonsurgical periodontal therapy on serum and gingival crevicular fluid cytokine levels during pregnancy and postpartum

BACKGROUND AND OBJECTIVE A low-grade systemic inflammatory status originating from periodontal infection has been proposed to explain the association between periodontal disease and systemic conditions, including adverse obstetric outcomes. The aim of this study was to evaluate the effect of periodontal therapy during pregnancy on the gingival crevicular fluid and serum levels of six cytokines associated with periodontal disease and preterm birth. MATERIAL AND METHODS A subsample of 60 women (18-35 years of age) up to 20 gestational weeks, previously enrolled in a larger randomized clinical trial, was recruited for the present study. Participants were randomly allocated to receive either comprehensive nonsurgical periodontal therapy before 24 gestational weeks (n = 30, test group) or only one appointment for supragingival calculus removal (n = 30, control group). Clinical data, and samples of blood and gingival crevicular fluid, were collected at baseline, at 26-28 gestational weeks and 30 d after delivery. The levels of interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70 and tumor necrosis factor-α were analyzed by flow cytometry. RESULTS After treatment, a major reduction in periodontal inflammation was observed in the test group, with bleeding on probing decreasing from 49.62% of sites to 11.66% of sites (p < 0.001). Periodontal therapy significantly reduced the levels of IL-1β and IL-8 in gingival crevicular fluid (p < 0.001). However, no significant effect of therapy was observed on serum cytokine levels. After delivery, the levels of IL-1β in the gingival crevicular fluid of the test group were significantly lower than were those in the control group (p < 0.001), but there were no significant differences between test and control groups regarding serum cytokine levels. CONCLUSION Although periodontal therapy during pregnancy successfully reduced periodontal inflammation and gingival crevicular fluid cytokine levels, it did not have a significant impact on serum biomarkers.

Brain‐derived neurotrophic factor and inflammatory markers in school‐aged children with early trauma

The impact of childhood trauma (CT) on brain‐derived neurotrophic factor (BDNF) and cytokines levels remains unclear. We investigated the association between CT and changes in BDNF and cytokines plasma levels in children.

Relationship between cytokine levels in serum and gingival crevicular fluid (GCF) in pregnant women

BACKGROUND Periodontal disease has been linked to systemic diseases/disorders and a low-grade systemic inflammatory status originated from periodontitis has been proposed as a possible explanation for this association. This study evaluates the relationship, early in pregnancy, between gingival crevicular fluid (GCF) and serum levels of a panel of cytokines that have been implicated in PTB and periodontal disease. METHODS One hundred pregnant women aged 18-35 years old with a gestational age up to 20 weeks were included (mean±SD gestational age:16.1±3.5 weeks). Four periodontal sites per subject were randomly selected for GCF collection. Serum and GCF levels of IL-1β, IL-6, IL-8, IL-10, IL-12p70 and TNF-α were analyzed using a cytometric bead array. Regression and correlation analyses were used to assess the relationship between serum and GCF cytokine levels. RESULTS Participants had widespread periodontal inflammation but limited periodontal destruction. Cytokine levels were significantly higher in GCF than serum for all cytokines but IL-10. GCF levels had small but significant effect on serum levels for IL-10 (β=0.34±0.09, p<0.01), IL-12p70 (β=0.48±0.08, p<0.01) and TNF-α (β=0.29±0.09, p<0.01). Periodontal probing depth and bleeding on probing were significantly associated with GCF levels for IL-1β, IL-6 and IL-8; however, they had negligible effect on serum cytokine levels. Correlation between GCF and serum levels was non-significant, except for IL-12p70, which showed a significant but small correlation between the two sources (r=0.32, p=0.001). CONCLUSIONS GCF cytokine levels were not strongly associated with serum cytokine levels in pregnant women with widespread periodontal inflammation but limited periodontal destruction.

Psychoneuroendocrine interventions aimed at attenuating immunosenescence: a review

There is evidence suggesting that immunosenescence can be accelerated by external factors such as chronic stress. Here we review potential psychoneuroendocrine determinants of premature aging of the immune system and discuss available interventions aimed at attenuating immunosenescence. Chronic stress may accelerate various features of immunosenescence by activating key allostatic systems, notably the hypothalamic–pituitary–adrenal axis. The immunological impact of such neuroendocrine dysregulation may be further amplified by a dramatic decline in dehydroepiandrosterone (DHEA) levels, acting in part as an endogenous glucocorticoid antagonist. Stress-buffering strategies show beneficial effects on various biomarkers in elderly populations. Likewise, supplementation of DHEA, melatonin or growth hormone has yielded significant beneficial effects in a number of studies, including: increased well-being, memory performance, bone mineral density and improved immunocompetence as evidenced by results of in vitro (T cell proliferation, cytotoxicity, cytokine production), and in vivo immune challenges. However, the side-effects of hormonal supplementation are also discussed. Finally, moderate exercise via the promotion of cortisol/DHEA balance or epigenetic modifications, is associated with lower serum pro-inflammatory cytokines, greater lymphoproliferative responses and lower counts of senescent T cells. Taken together, these data suggest that immune system is plastic and immunosenescence can be attenuated psychoneuroendocrine interventions.

Association Between Mannose-Binding Lectin Gene Polymorphisms and Pre-eclampsia in Brazilian Women

Citation Vianna P, da Silva GK, dos Santos BP, Bauer ME, Dalmáz CA, Bandinelli E, Chies JAB. Association between Mannose‐Binding Lectin gene polymorphisms and pre‐eclampsia in Brazilian Women. Am J Reprod Immunol 2010

HLA-G and CD8+ regulatory T cells in the inflammatory environment of pre-eclampsia

During pregnancy, the maternal immune system is tolerant to foetal antigens via the engagement of immune regulatory mechanisms. Failure in regulating the maternal immunity to foetal antigens may lead to pre-eclampsia (PE). We addressed the role of HLA-G gene polymorphisms and protein expression as well as regulatory T cells and Th1/Th2/Th17 cytokines in healthy and pathological pregnancies. Blood samples from 26 pregnant women with PE, 25 non-PE and 7 strictly healthy pregnant women were assessed. PBMCs were phenotyped for early activation markers (CD25 and CD69), regulatory T-cell markers (CD8+CD28- and CD4+CD25highFoxp3+), ILT-2 (HLA-G receptor) and HLA-G. Lymphocyte proliferation was estimated and levels of IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α and IL-17 were measured. HLA-G polymorphisms (rs66554220 and rs1063320) were genotyped by PCR. PE women exhibited low levels of HLA-G in PBMCs and low frequency of regulatory CD8+CD28- T cells. High amounts of the pro-inflammatory cytokines IL-17, IL-2 and TNF-α as well as IL-4 and IL-10 and an increased proliferative cell activation profile were observed in PE. The allelic and genotypic frequencies of the HLA-G gene polymorphisms and the frequency of CD4+CD25highFoxp3+ T cells did not vary among the groups. Our data suggest that the cytokine imbalance presented in PE is associated with a deficient immune regulatory profile, contributing to an impaired immune tolerance between mother and foetus.

Taurine counteracts the neurotoxic effects of streptozotocin-induced diabetes in rats

Diabetes is a chronic metabolic disease associated with oxidative stress, damage to biomolecules such as DNA, and neuroinflammation. Taurine, a sulfur-containing amino acid widespread in the brain, has neuroprotective properties that might prevent tissue injury and DNA damage induced by chronic hyperglycemia. We evaluated the effects of chronic taurine treatment on oxidative stress parameters, DNA damage and inflammatory markers in the frontal cortex, and hippocampus of streptozotocin-induced diabetic rats. Diabetic rats displayed increased levels of reactive oxygen species (ROS) and DNA damage in both areas, evidencing the pro-oxidant effects of diabetes in the brain. Moreover, this condition increased levels of several inflammatory mediators, such as IL-6, IL-12, TNF-γ, and IFN-α, more pronouncedly in the hippocampus. Supporting our hypothesis, taurine treatment reduced ROS, DNA damage, and inflammatory cytokine levels, providing evidence of its beneficial effects against genotoxicity and neuroinflammation associated with diabetes. Our data endorse the necessary clinical trials to evaluate the efficacy and safety of taurine supplementation in the prevention and treatment of neurochemical and metabolic alterations related to diabetes.