-
European Journal of Medical Research Aug 2023We sought to determine the extent to which cortisol suppressed innate and T cell-mediated cytokine production and whether it could be involved in reducing peripheral...
BACKGROUND
We sought to determine the extent to which cortisol suppressed innate and T cell-mediated cytokine production and whether it could be involved in reducing peripheral cytokine production following subarachnoid haemorrhage (SAH).
METHODS
Whole blood from healthy controls, patients with SAH and healthy volunteers was stimulated with lipopolysaccharide (LPS), to stimulate innate immunity, or phytohaemagglutinin (PHA), to stimulate T cell-mediated immunity. Varying concentrations of cortisol were included, with or without the cortisol antagonist RU486. Concentration of interleukin-6 (IL-6), IL-1β and tumour necrosis factor-alpha) TNFα were determined as a measure of innate immunity. IL-6, IL-17 (interferon gamma) IFNƔ and IL-17 were determined as an indicator of T cell-mediated immunity.
RESULTS
Suppression of innate responses to LPS was apparent in whole blood from SAH patients, relative to healthy controls, and TNFα production was inversely correlated with plasma cortisol concentration. Cytokine production in whole blood from healthy volunteers was inhibited by cortisol concentrations from 0.33 µM, or 1 µM and above, and these responses were effectively reversed by the cortisol antagonist RU-486. In SAH patients, RU-486 reversed suppression of innate TNF-α and IL-6 responses, but not IL-1ß or T cell-mediated responses.
CONCLUSION
These data suggest that cortisol may play a role in reducing innate, but not T cell-mediated immune responses in patients with injuries such as SAH and that cortisol antagonists could be effective in boosting early innate responses.
Topics: Humans; Hydrocortisone; Interleukin-17; Interleukin-6; Lipopolysaccharides; Mifepristone; Subarachnoid Hemorrhage; Tumor Necrosis Factor-alpha; Immunosuppression Therapy; Interferon-gamma
PubMed: 37644600
DOI: 10.1186/s40001-023-01222-3 -
The Journal of Comparative Neurology Feb 2023The orbital cortex (ORB) of the rat consists of five divisions: the medial (MO), ventral (VO), ventrolateral (VLO), lateral (LO), and dorsolateral (DLO) orbital...
The orbital cortex (ORB) of the rat consists of five divisions: the medial (MO), ventral (VO), ventrolateral (VLO), lateral (LO), and dorsolateral (DLO) orbital cortices. No previous report has comprehensively examined and compared projections from each division of the ORB to the thalamus. Using the anterograde anatomical tracer, Phaseolus vulgaris leucoagglutinin, we describe the efferent projections from the five divisions of the ORB to the thalamus in the rat. We demonstrated that, with some overlap, each division of the ORB distributed in a distinct (and unique) manner to nuclei of the thalamus. Overall, ORB projected to a relatively restricted number of sites in the thalamus, and strikingly distributed entirely to structures of the medial/midline thalamus, while completely avoiding lateral regions or principal nuclei of the thalamus. The main termination sites in the thalamus were the paratenial nucleus (PT) and nucleus reuniens (RE) of the midline thalamus, the medial (MDm) and central (MDc) divisions of the mediodorsal nucleus, the intermediodorsal nucleus, the central lateral, paracentral, and central medial nuclei of the rostral intralaminar complex and the submedial nucleus (SM). With some exceptions, medial divisions of the ORB (MO, VO) mainly targeted "limbic-associated" nuclei such as PT, RE, and MDm, whereas lateral division (VLO, LO, DLO) primarily distributed to "sensorimotor-associated" nuclei including MDc, SM, and the rostral intralaminar complex. As discussed herein, the medial/midline thalamus may represent an important link (or bridge) between the orbital cortex and the hippocampus and between the ORB and medial prefrontal cortex. In summary, the present results demonstrate that each division of the orbital cortex projects in a distinct manner to nuclei of the thalamus which suggests unique functions for each division of the orbital cortex.
Topics: Animals; Rats; Prefrontal Cortex; Thalamus; Midline Thalamic Nuclei; Hippocampus; Intralaminar Thalamic Nuclei; Phytohemagglutinins; Neural Pathways
PubMed: 36226328
DOI: 10.1002/cne.25419 -
Journal of Investigative Medicine : the... Jan 2021Genital inflammation is an established risk factor for increased HIV acquisition risk. Certain HIV-exposed seronegative populations, who are naturally resistant to HIV...
Genital inflammation is an established risk factor for increased HIV acquisition risk. Certain HIV-exposed seronegative populations, who are naturally resistant to HIV infection, have an immune quiescent phenotype defined by reduced immune activation and inflammatory cytokines at the genital tract. Therefore, the aim of this study was to create an immune quiescent environment using immunomodulatory drugs to mitigate HIV infection. Using an peripheral blood mononuclear cell (PBMC) model, we found that inflammation was induced using phytohemagglutinin and Toll-like receptor (TLR) agonists Pam3CSK4 (TLR1/2), lipopolysaccharide (LPS) (TLR4) and R848 (TLR7/8). After treatment with anti-inflammatory drugs, ibuprofen (IBF) and betamethasone (BMS), PBMCs were exposed to HIV NL4-3 AD8. Multiplexed ELISA was used to measure 28 cytokines to assess inflammation. Flow cytometry was used to measure immune activation (CD38, HLA-DR and CCR5) and HIV infection (p24 production) of CD4+ T cells. BMS potently suppressed inflammation (soluble cytokines, p<0.05) and immune activation (CD4+ T cells, p<0.05). BMS significantly reduced HIV infection of CD4+ T cells only in the LPS (0.98%) and unstimulated (1.7%) conditions (p<0.02). In contrast, IBF had minimal anti-inflammatory and immunosuppressive but no anti-HIV effects. BMS demonstrated potent anti-inflammatory effects, regardless of stimulation condition. Despite uniform immunosuppression, BMS differentially affected HIV infection according to the stimulation conditions, highlighting the complex nature of these interactions. Together, these data underscore the importance of interrogating inflammatory signaling pathways to identify novel drug targets to mitigate HIV infection.
Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Betamethasone; CD4-Positive T-Lymphocytes; Cells, Cultured; Disease Transmission, Infectious; Female; HIV; HIV Infections; Humans; Ibuprofen; Immunosuppression Therapy; In Vitro Techniques; Leukocytes, Mononuclear; Phytohemagglutinins; Toll-Like Receptors
PubMed: 33004468
DOI: 10.1136/jim-2020-001424 -
Frontiers in Immunology 2021The differential diagnosis between tuberculous meningitis (TBM) and bacterial meningitis (BM) remains challenging in clinical practice. This study aimed to establish a...
BACKGROUND
The differential diagnosis between tuberculous meningitis (TBM) and bacterial meningitis (BM) remains challenging in clinical practice. This study aimed to establish a diagnostic model that could accurately distinguish TBM from BM.
METHODS
Patients with TBM or BM were recruited between January 2017 and January 2021 at Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort). The detection for indicators involved in cerebrospinal fluid (CSF) and T-SPOT assay were performed simultaneously. Multivariate logistic regression was used to create a diagnostic model.
RESULTS
A total of 174 patients (76 TBM and 98 BM) and another 105 cases (39 TBM and 66 BM) were enrolled from Qiaokou cohort and Caidian cohort, respectively. Significantly higher level of CSF lymphocyte proportion while significantly lower levels of CSF chlorine, nucleated cell count, and neutrophil proportion were observed in TBM group when comparing with those in BM group. However, receiver operating characteristic (ROC) curve analysis showed that the areas under the ROC curve (AUCs) produced by these indicators were all under 0.8. Meanwhile, tuberculosis-specific antigen/phytohemagglutinin (TBAg/PHA) ratio yielded an AUC of 0.889 (95% CI, 0.840-0.938) in distinguishing TBM from BM, with a sensitivity of 68.42% (95% CI, 57.30%-77.77%) and a specificity of 92.86% (95% CI, 85.98%-96.50%) when a cutoff value of 0.163 was used. Consequently, we successfully established a diagnostic model based on the combination of TBAg/PHA ratio, CSF chlorine, CSF nucleated cell count, and CSF lymphocyte proportion for discrimination between TBM and BM. The established model showed good performance in differentiating TBM from BM (AUC: 0.949; 95% CI, 0.921-0.978), with 81.58% (95% CI, 71.42%-88.70%) sensitivity and 91.84% (95% CI, 84.71%-95.81%) specificity. The performance of the diagnostic model obtained in Qiaokou cohort was further validated in Caidian cohort. The diagnostic model in Caidian cohort produced an AUC of 0.923 (95% CI, 0.867-0.980) with 79.49% (95% CI, 64.47%-89.22%) sensitivity and 90.91% (95% CI, 81.55%-95.77%) specificity.
CONCLUSIONS
The diagnostic model established based on the combination of four indicators had excellent utility in the discrimination between TBM and BM.
Topics: Adult; Antigens, Bacterial; Biomarkers; Cerebrospinal Fluid; China; Cohort Studies; Diagnosis, Differential; Enzyme-Linked Immunospot Assay; Female; Humans; Interferon-gamma; Male; Meningitis, Bacterial; Middle Aged; Models, Biological; Mycobacterium tuberculosis; Tuberculosis, Meningeal
PubMed: 34867952
DOI: 10.3389/fimmu.2021.731876 -
Molecules (Basel, Switzerland) Aug 2020The synthesis of a series of novel 7-aminooxazolo[5,4-]pyrimidines , transformations during their synthesis and their physicochemical characteristics have been...
The synthesis of a series of novel 7-aminooxazolo[5,4-]pyrimidines , transformations during their synthesis and their physicochemical characteristics have been described. Complete detailed spectral analysis of the intermediates -, the -cyanooxazolylacetamidine by-products and final compounds has been carried out using MS, IR, 1D and 2D NMR spectroscopy. Theoretical research was carried out to explain the privileged formation of 7-aminooxazolo[5,4-]pyrimidines in relation to the possibility of their isomer formation and the related thermodynamic aspects. Additionally, the single-crystal X-ray diffraction analysis for was reported. Ten 7-aminooxazolo[5,4-]pyrimidines (-) were biologically tested in vitro to preliminarily evaluate their immunological, antiviral and anticancer activity. Compounds and showed the best immunoregulatory profile. The compounds displayed low-toxicity and strongly inhibited phytohemagglutinin A-induced proliferation of human peripheral blood lymphocytes and lipopolysaccharide-induced proliferation of mouse splenocytes. Compound caused also a moderate suppression of tumor necrosis factor α (TNF-α) production in a human whole blood culture. Of note, the compounds also inhibited the growth of selected tumor cell lines and inhibited replication of human herpes virus type-1 (HHV-1) virus in A-549 cell line. Molecular investigations showed that the compounds exerted differential changes in expression of signaling proteins in Jurkat and WEHI-231 cell lines. The activity of is likely associated with elicitation of cell signaling pathways leading to cell apoptosis. The compounds may be of interest in terms of therapeutic utility as inhibitors of autoimmune disorders, virus replication and antitumor agents.
Topics: Blood Cells; Chemical Phenomena; Chemistry Techniques, Synthetic; Humans; Hydrogen Bonding; Lymphocytes; Models, Molecular; Molecular Conformation; Molecular Structure; Oxazoles; Pyrimidines; Signal Transduction; Structure-Activity Relationship; Tumor Necrosis Factor-alpha
PubMed: 32759841
DOI: 10.3390/molecules25153558 -
Biology Nov 2022Although impaired mitochondrial function has been proposed as a hallmark of multiple sclerosis (MS) disease, few studies focus on the mitochondria of immune cells. We...
Although impaired mitochondrial function has been proposed as a hallmark of multiple sclerosis (MS) disease, few studies focus on the mitochondria of immune cells. We aimed to compare the mitochondrial function of the peripheral blood mononuclear cells (PBMCs) from MS patients with (M+) and without (M-) lipid-specific oligoclonal immunoglobulin M bands (LS-OCMB), and healthydonors (HD). We conducted an exploratory cross-sectional study with 19 untreated MS patients (M+ = 9 and M- = 10) and 17 HDs. Mitochondrial superoxide anion production and mitochondrial mass in PBMCs were assessed without and with phytohemagglutinin by flow cytometry. The PBMCs' mitochondrial function was analyzed using Seahorse technology. Superoxide anion production corrected by the mitochondrial mass was higher in MS patients compared with HDs ( = 0.011). Mitochondrial function from M+ patients showed some impairments compared with M- patients. Without stimulus, we observed higher proton leak ( = 0.041) but lower coupling efficiency ( = 0.041) in M+ patients; and under stimulation, lower metabolic potential ECAR ( = 0.011), and lower stressed OCR/ECAR in the same patients. Exclusively among M+ patients, we described a higher mitochondrial dysfunction in the oldest ones. The mitochondrial impairments found in the PBMCs from MS patients, specifically in M+ patients, could help to better understand the disease's physiopathology.
PubMed: 36358334
DOI: 10.3390/biology11111633 -
Tropical Animal Health and Production Nov 2020The current study was conducted to evaluate the anti-mycotoxigenic effects of previously isolated Bacillus spp. in Japanese quails. A total of 240-day-old Japanese...
The current study was conducted to evaluate the anti-mycotoxigenic effects of previously isolated Bacillus spp. in Japanese quails. A total of 240-day-old Japanese quails were assigned in to six treatments and four replicates. Dietary treatments included the following: negative control (basal diet), positive control (basal diet + 2.5 ppm afltatoxin B), probiotic treatments (basal diet + 2.5 ppm afltatoxin B), and 10 cfu/ml of different Bacillus spp. (B. megaterium, B. subtilis, or B. laterosporus) in drinking water and treatment P (basal diet + 2.5 ppm afltatoxin B and 2.5 ppm Polysorb®). Body weight gain, feed intake, and feed conversion ratio were not affected by dietary treatments (P > 0.05). Carcass yield significantly increased in B. megaterium and B. subtilis treatments compared with positive control. Supplementation of B. megaterium significantly increased testes, uterus and oviduct weights, skin response to 2,4-dinitro 1-chlorobenzene and phytohemagglutinin, and antibody production against sheep red blood cells (P < 0.05). B. megaterium could significantly increase bursa weight and decrease liver weight compared with positive control (P < 0.05). B. megaterium, B. laterosporus, and Polysorb treatments significantly decreased H:L and aspartate aminotransferase activity in aflatoxin B fed control (P < 0.05). B. megaterium and B. laterosporus significantly increased tibia weight, length, radius, index, and ash content compared with positive control (P < 0.05). All dietary additives significantly reduced meat oxidation, total aerobic bacteria, and spore forming bacteria of ileal content compared with positive control (P < 0.05). Ileal lactic acid bacteria significantly increased in B. megaterium treatment (P < 0.05). Totally, B. megaterium might be a promising probiotic with a comparable afltatoxin B removal potential to commercial toxin binder (Polysorb).
Topics: Aflatoxin B1; Animal Feed; Animals; Bacillus; Coturnix; Diet; Probiotics
PubMed: 32946023
DOI: 10.1007/s11250-020-02223-8 -
Archivos de Bronconeumologia Sep 2022The clinical and epidemiological implications of abnormal immune responses in COVID-19 for latent tuberculosis infection (LTBI) screening are unclear. (Review)
Review
Clinical and Epidemiological Correlates of Low IFN-Gamma Responses in Mitogen Tube of QuantiFERON Assay in Tuberculosis Infection Screening During the COVID-19 Pandemic: A Population-Based Marker of COVID-19 Mortality?
BACKGROUND
The clinical and epidemiological implications of abnormal immune responses in COVID-19 for latent tuberculosis infection (LTBI) screening are unclear.
METHODS
We reviewed QuantiFERON TB Gold Plus (QFT-Plus) results (36,709 patients) from July 2016 until October 2021 in Asturias (Spain). We also studied a cohort of ninety hospitalized patients with suspected/confirmed COVID-19 pneumonia and a group of elderly hospitalized patients with COVID-19 who underwent serial QFT-Plus and immune profiling testing.
RESULTS
The indeterminate QFT-Plus results rate went from 1.4% (July 2016 to November 2019) to 4.2% during the COVID-19 pandemic. The evolution of the number of cases with low/very low interferon-gamma (IFN-gamma) response in the mitogen tube paralleled the disease activity and number of deaths during the pandemic waves in our region (from March 2020 to October 2021). The percentages of positive QFT-plus patients did not significantly change before and during the pandemic (13.9% . 12.2%). Forty-nine patients from the suspected/confirmed COVID-19 pneumonia cohort (54.4%) had low/very low IFN-gamma response to mitogen, 22 of them (24.4%) had severe and critical pneumonia. None received immunosuppressants prior to testing. Abnormal radiological findings (P = 0.01) but not COVID-19 severity was associated with low mitogen response. Immune profiling showed a reduction of CD8 + T cells and a direct correlation between the number of EMRA CD8 + T-cells and IFN-gamma response to mitogen (P = 0.03).
CONCLUSION
Low IFN-gamma responses in mitogen tube of QFT-Plus often occur in COVID-19 pneumonia, which is associated with a low number of an effector CD8 + T-cell subset and does not seem to affect LTBI screening; however, this abnormality seems to parallel the dynamics of COVID-19 at the population level and its mortality.
Topics: Aged; Biomarkers; COVID-19; Humans; Interferon-gamma; Interferon-gamma Release Tests; Latent Tuberculosis; Mitogens; Mycobacterium tuberculosis; Pandemics; Tuberculin Test
PubMed: 35185258
DOI: 10.1016/j.arbres.2022.01.011 -
Iranian Journal of Microbiology Oct 2022Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. Peripheral blood monocytes cells (PBMCs) may have altered function to some...
BACKGROUND AND OBJECTIVES
Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. Peripheral blood monocytes cells (PBMCs) may have altered function to some extent in women with endometriosis. is a probiotic bacterium within the human body with the ability of alleviating many inflammatory diseases. Here, we examined the effect of on PBMCs of endometriosis patients.
MATERIALS AND METHODS
In this study, peripheral blood samples were obtained from endometriosis patients (n=11) and non-endometriosis individuals (n=11). After isolation of peripheral blood mononuclear cells with Ficoll, cells were cultured in the presence and absence of phytohemagglutinin. Also, these cells were co-cultured with 1×10 CFU/ml of IL-6 and IL-1 cytokines were measured by ELISA method and the two groups were evaluated and compared.
RESULTS
The results showed that in endometriosis patients, the production of pro-inflammatory cytokines, including IL-1 and IL-6, by PBMC was increased compared to non-endometriosis subjects, and stimuli such as PHA intensified this elevation. Also, increased the levels of pro-inflammatory cytokines including IL-1 and IL-6. However, the production of these cytokines decreased due to the modulatory properties of bacterial cells after 48 h.
CONCLUSION
According to the results of the current study, IL-1 and IL-6 production was significantly increased in PMBCs of endometriosis patients compared to that of the healthy controls. Also, was considered as an antigenic compound and induced IL-1 and IL-6 production. According to these results, probiotics can be further used for the treatment of endometriosis patients and more investigations are needed to confirm these results.
PubMed: 36531824
DOI: 10.18502/ijm.v14i5.10965 -
Frontiers in Immunology 2021Unique Individuals who exhibit either suppressive HIV-1 control, or the ability to maintain low viral load set-points and preserve their CD4+ T cell counts for extended...
Unique Individuals who exhibit either suppressive HIV-1 control, or the ability to maintain low viral load set-points and preserve their CD4+ T cell counts for extended time periods in the absence of antiretroviral therapy, are broadly termed HIV-1 controllers. We assessed the extent to which black South African controllers (n=9), differ from uninfected healthy controls (HCs, n=22) in terms of lymphocyte and monocyte CCR5 expression (density and frequency of CCR5-expressing cells), immune activation as well as peripheral blood mononuclear cell (PBMC) mitogen-induced chemokine/cytokine production. In addition, relative CD4+ T cell CCR5 mRNA expression was assessed in a larger group of controllers (n=20) compared to HCs (n=10) and HIV-1 progressors (n=12). Despite controllers having significantly higher frequencies of activated CD4+ and CD8+ T cells (HLA-DR+) compared to HCs, CCR5 density was significantly lower in these T cell populations (=0.039 and =0.064, respectively). This lower CCR5 density was largely attributable to controllers with higher VLs (>400 RNA copies/ml). Significantly lower CD4+ T cell CCR5 density in controllers was maintained (=0.036) when HCs (n=12) and controllers (n=9) were matched for age. CD4+ T cell CCR5 mRNA expression was significantly less in controllers compared to HCs (=0.007) and progressors (=0.002), whereas HCs and progressors were similar (=0.223). The levels of soluble CD14 in plasma did not differ between controllers and HCs, suggesting no demonstrable monocyte activation. While controllers had lower monocyte CCR5 density compared to the HCs (=0.02), significance was lost when groups were age-matched (=0.804). However, when groups were matched for both CCR5 promoter haplotype and age (n=6 for both) reduced CCR5 density on monocytes in controllers relative to HCs was highly significant (=0.009). Phytohemagglutinin-stimulated PBMCs from the controllers produced significantly less CCL3 (=0.029), CCL4 (=0.008) and IL-10 (P=0.028) compared to the HCs, which was largely attributable to the controllers with lower VLs (<400 RNA copies/ml). Our findings support a hypothesis of an inherent (genetic) predisposition to lower CCR5 expression in individuals who naturally control HIV-1, as has been suggested for Caucasian controllers, and thus, likely involves a mechanism shared between ethnically divergent population groups.
Topics: Adult; Black People; Disease Resistance; Female; HIV Infections; HIV-1; Humans; Male; Middle Aged; Receptors, CCR5; South Africa; T-Lymphocytes
PubMed: 34987508
DOI: 10.3389/fimmu.2021.781263