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Sexual activity modulates shifts in TH1/TH2 cytokine profile across the menstrual cycle: an observational study.

ABSTRACT: OBJECTIVE:To investigate if sexual activity moderated menstrual cycle-related shifts in cytokines associated with T-helper type 1 (TH1) cells (e.g., interferon [IFN] ?) and T-helper type 2 (TH2) cells (e.g., interleukin [IL] 4). Immune activity shifts across the menstrual cycle, with higher follicular-phase TH1-cell activity but higher luteal-phase TH2-cell activity. Little is known about how social behaviors alter TH1-TH2 ratios, despite evidence that psychosocial factors can influence immunity. Of particular interest is how sexual activity influences immune responses that may support conception, such as the TH1-TH2 balance. DESIGN:Participants provided saliva samples at four time points (menstrual, follicular, ovulatory, and luteal phases), which were assayed by means of ELISA. SETTING:Academic laboratory. PARTICIPANT(S):Thirty healthy premenopausal women (16 sexually abstinent, 14 sexually active) not taking hormonal or immunoactive medications. INTERVENTION(S):None. MAIN OUTCOME MEASURE(S):Salivary E2, P, IFN-?, and IL-4. RESULT(S):Sexually active, but not abstinent, women were significantly more likely to express TH2-like cytokine ratios (IFN-? < IL-4) in the luteal phase than in other phases. Similarly, sexually active women had significantly higher P, and higher P-E2 ratios, in the luteal phase than did abstinent women. The P-E2 ratio mediated menstrual variations in cytokine ratios in sexually active women. CONCLUSION(S):These results support the hypothesis that shifts in immune response across the menstrual cycle may reflect tradeoffs between reproduction and immunity. These findings point to the need for further research on the interaction between sexual behavior, the menstrual cycle, and immune response.

SUBMITTER: Lorenz TK

PROVIDER: S-EPMC4663173 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Sexual activity modulates shifts in TH1/TH2 cytokine profile across the menstrual cycle: an observational study.

Lorenz Tierney K TK Heiman Julia R JR Demas Gregory E GE

Fertility and sterility 20150916 6

<h4>Objective</h4>To investigate if sexual activity moderated menstrual cycle-related shifts in cytokines associated with T-helper type 1 (TH1) cells (e.g., interferon [IFN] γ) and T-helper type 2 (TH2) cells (e.g., interleukin [IL] 4). Immune activity shifts across the menstrual cycle, with higher follicular-phase TH1-cell activity but higher luteal-phase TH2-cell activity. Little is known about how social behaviors alter TH1-TH2 ratios, despite evidence that psychosocial factors can influence ...[more]

PMID: 26385401

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Project description:IntroductionThe menstrual cycle is regulated by a complex interplay between endometrial epithelial cells, endothelial cells, immune cells, and sex hormones. To communicate, cells secrete cytokines that have multiple and diverse effects on recipient cells. Knowledge of how these cells interact in the uterus is insufficient. Menstrual blood is easily accessible and provides a source to study menstrual cycle physiology. This study aimed to determine the cytokine profile in menstrual blood plasma and investigate the differences in cytokine profiles between menstrual and peripheral blood plasma. Several previous studies indicate an improved chance of embryo implantation after endometrial scratching. Consequently, our secondary aim was to compare the menstrual blood cytokine profile before and after luteal phase endometrial scratching.Material and methodsNineteen healthy donors collected menstrual blood for the first 24 hours of menstruation in two sequential cycles. Matched peripheral blood was taken at the same time. An endometrial biopsy was performed at cycle day 7-9 post ovulation in between the two collection times. A Luminex multiplex assay was performed in one batch analyzing a predetermined group of cytokines in plasma.ResultsPeripheral blood plasma and menstrual blood plasma showed substantial significant differences in cytokine profile. In menstrual blood plasma, C5/C5a, interleukin-6 (IL-6), IL-1β, and CXCL8 were detected in high concentrations, whereas IL-2, IL-12p70, XCL1/Lymphotactin, and interferon-γ were low. The most pronounced median differences between menstrual and peripheral blood plasma were found for IL-6, IL-1β, and CXCL8. The cytokine profiles of menstrual blood plasma were similar between the individual donors and did not differ over two subsequent cycles. None of the cytokines analyzed in menstrual blood plasma differed significantly before or after luteal phase endometrial scratching (P < .01).ConclusionsOur results demonstrate that the menstrual blood cytokine profile is distinctly different from peripheral blood plasma and that the inter-individual difference in menstrual blood cytokine profile in healthy donors is limited and stable over time. The small injury caused by an endometrial biopsy does not change the cytokine profile in the subsequent menstrual cycle. Our study provides new insights into menstrual cycle physiology.

Project description:Background: Chronic periodontitis (CP), caused by bacteria and fungi, appears in up to 66% of HIV-patients. The impact and association of HIV-treatment (HAART) and Candida itself has not been properly evaluated in the development and progression of CP. The immunopathogenesis is characterized by CD4+ T-cells activation and the balance between the T-helper 1 (Th1) and T-helper 2 (Th2) or a mixed cytokine profile. Currently, the associated causes of an immune response in HIV-patients with CP is controversial. Our aims were the determination of Candida spp. and cytokine profile in oral samples from HIV-positive patients with CP, considering the CD4+ T cells levels and HAART use. Methods: From 500 HIV-positive patients evaluated, 228 patients were enrolled. Patients were separated in groups: (A) n = 53 (≤200 CD4+ T-cells on HAART); (B) n = 57 (≤200 CD4+ T-cells without HAART); (C) n = 50 (>200 CD4+ T-cells without HAART); (D) n = 68 (>200 CD4+ T-cells on HAART). Candida spp. were isolated from the oral biofilm and crevicular fluid in CHROMagar and confirmed by endpoint PCR. Cytokine levels were measured by beads-based immunoassay in saliva by flow cytometry. Results: 147 patients (64.5%) were positive to Candida spp. and 204 strains were isolated; 138 (67.6%) were C. albicans and the remaining C. non-albicans species (C. glabrata>C. tropicalis>C. krusei>C. dubliniensis). In this study, CHROMagar showed good sensitivity (95%) but poor specificity (68%); since of the 152 samples identified as C. albicans, only 131 were confirmed by PCR; from the 10 samples identified as C. glabrata, only six were confirmed. Finally, of the 42 samples detected as C. tropicalis, only five were confirmed. When evaluating Candida spp. presence, group A and D had higher isolation, while group B had the highest species diversity. Whereas, group C had a significant reduction of Candida spp. Despite the presence of Candida and HAART, we found a Th1/Th2 hybrid profile in the saliva of patients with low CD4+ T-cell count (group A). Conclusion: Abundance and diversity of the Candida spp. detected in HIV-patients with CP could be related to HAART and low CD4+ T-cells levels. Also, the immunosuppression might promote a local Th1/Th2 hybrid cytokine profile.

Project description:A major component of COVID-19 severe respiratory syndrome is the patient's immune response to the SARS-CoV-2 virus and the consequential multi-organ inflammatory response. Several studies suggested a potential role of CD4+ T cells in COVID-19 severe respiratory syndrome. We first hypothesized that there is a type 2 helper (Th2)/type 1 helper (Th1) imbalance in older age, male, asthma, smokers, and high ACE2 expression phenotype in the airway of non-infected patients. Next, we hypothesized that a Th2/Th1 imbalance may predict higher mortality in COVID-19 infected hospitalized patients with and without patient reported current asthma. We first analyzed publicly available gene expression from the sputum of 118 moderate-to-severe asthma patients and 21 healthy controls, and from nasal epithelium of 26 healthy current smokers and 21 healthy never smokers. Secondly, we profiled 288 new serum proteomics samples measured at admission from patients hospitalized within the Mount Sinai Health System with positive SARS-CoV-2 infection. We first computed Th1 and Th2 pathway enrichment scores by gene set variation analysis and then compared the differences in Th2 and Th1 pathway scores between patients that died compared to those that survived, by linear regression. The level of Th2/Th1 imbalance, as determined by the enrichment score, was associated with age, sex, and ACE2 expression in sputum, and with active smoking status in nasal epithelium (p < 0.05). Th2/Th1 imbalance at hospital admission in sera of patients was not significantly associated with death from COVID-19 (p = 0.11), unless evaluated in the asthmatic strata (p = 0.01). Using a similar approach we also observed a higher Th17/Th1 cytokine imbalance in all deceased patients compared to those that survived (p < 0.001), as well as in the asthmatic strata only (p < 0.01). Th2/Th1 imbalance is higher in the sera of asthma patients at admission that do not survive COVID-19, suggesting that the Th2/Th1 interplay may affect patient outcomes in SARS-CoV2 infection. In addition, we report that Th17/Th1 imbalance is increased in all patients that die of COVID-19.

Project description:BackgroundHaemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of immune regulation, and HLH patients with mutations in genes including PRF1, UNC13D, STX11, STXBP2, SH2D1A, XIAP, and ITK were reported to be primary HLH. Due to the different treatment options, the differentiation between primary and secondary HLH is critical. Our previous studies have showed that a Th1/Th2 cytokine profile is diagnostic for HLH, yet the cytokine profiles between primary and secondary HLH have not been compared. The aim of the study was to test whether the Th1/Th2 cytokine profile could be used as a tool to differentiate between primary and secondary HLH.MethodsA total of 45 hospitalized Chinese children with HLH during the period of February 2010 through September 2012 were enrolled in the study. Fifty healthy children were enrolled as controls. Primary HLH related genes were sequenced using genomic DNA samples. The Th1/Th2 cytokine levels including interferon-γ (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-10, IL-6, IL-4 and IL-2 were quantitatively determined by cytometric bead assay techniques.ResultsPrimary HLH group (n = 4) included one patient with biallelic heterozygous mutations in PRF1 gene, and three patients with hemizygous mutation in SH2D1A gene. Based on the available genetic data, the other 41 patients were classified into the secondary HLH group. When compared the cytokine levels between the two groups, IL-4 level in primary-HLH was significantly lower than that in secondary HLH (P = 0.025), while IFN-γ level in primary HLH had a tendency of statistically lower than that in secondary HLH (P = 0.051). Area under receiver operating characteristic (ROC) curves of IL-4 and IFN-γ, IL-10, TNF-α, IL-2, and IL-6 levels were 0.841, 0.799, 0.506, 0.494, 0.457, and 0.250, respectively. ROC curves showed that 1.7 pg/ml of IL-4 had sensitivity and specificity for differentiation between primary and secondary HLH as 70.7 and 100.0 %, while 433.9 pg/ml of IFN-γ had sensitivity and specificity as 51.2 and 100.0 %, respectively.ConclusionsHLH patients with lower IL-4 and IFN-γ levels have higher possibility to be primary HLH. The cytokine profile may be used as an additional tool for the quick differential diagnosis between primary and secondary HLH.

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Sexual activity modulates shifts in TH1/TH2 cytokine profile across the menstrual cycle: an observational study.

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Sexual activity modulates shifts in TH1/TH2 cytokine profile across the menstrual cycle: an observational study.

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