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Journal of Neural Transmission (Vienna,... Jan 2015Lithium is an important psychopharmacological agent for the treatment of unipolar as well as bipolar affective disorders. Lithium has a number of side effects such as...
Lithium is an important psychopharmacological agent for the treatment of unipolar as well as bipolar affective disorders. Lithium has a number of side effects such as hypothyroidism and aggravation of psoriasis. On the other hand, lithium has pro-inflammatory effects, which appear beneficial in some disorders associated with immunological deficits, such as human immunodeficiency virus (HIV) infection and systemic lupus erythematosus (SLE). Therefore, immunological characteristics of lithium may be an important consideration in individualized therapeutic decisions. We measured the levels of the cytokines interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-22, IL-17 and tumour necrosis factor (TNF)-α in the stimulated blood of thirty healthy subjects supplemented with lithium alone, the antidepressants citalopram, escitalopram or mirtazapine alone, the combination of each antidepressant with lithium, and a no drug control. These drugs were tested under three blood stimulant conditions: murine anti-human CD3 monoclonal antibody OKT3 and the 5C3 monoclonal antibody (OKT3/5C3), phytohemagglutinin (PHA), and unstimulated blood. Lithium, alone and in combination with any of the tested antidepressants, led to a consistent increase of IL-1ß, IL-6 and TNF-α levels in the unstimulated as well as the stimulated blood. In the OKT3/5C3- and PHA-stimulated blood, IL-17 production was significantly enhanced by lithium. Lithium additionally increased IL-2 concentrations significantly in PHA-stimulated blood. The data support the view that lithium has pro-inflammatory properties. These immunological characteristics may contribute to side effects of lithium, but may also explain its beneficial effects in patients suffering from HIV infection or SLE.
Topics: Adult; Antidepressive Agents; Blood Cells; Cytokines; Dose-Response Relationship, Drug; Female; Flow Cytometry; Humans; Immunosuppressive Agents; Lithium; Male; Middle Aged; Mitogens; Muromonab-CD3; Phytohemagglutinins; Statistics, Nonparametric; Time Factors; Young Adult
PubMed: 25377522
DOI: 10.1007/s00702-014-1328-6 -
Journal of Cellular Biochemistry Apr 2019In vitro human lymphocyte culture methodology is well established yet certain confounding factors such as age, medical history as well as individual's blood type may...
In vitro human lymphocyte culture methodology is well established yet certain confounding factors such as age, medical history as well as individual's blood type may potentially modulate in vitro proliferation response. These factors have to be carefully evaluated to release reliable test report in routine cytogenetic evaluation for various genetic conditions, radiation biodosimetry, etc. With this objective, the current study was focused on analyzing the proliferation response of lymphocytes drawn from 90 individuals (21-29 years) with different blood types. The proliferation response was assessed in the cultured lymphocytes by cell cycle, mitotic index (MI), and nuclear division index (NDI) after stimulation with phytohaemagglutinin (PHA). To investigate the toxic effect on proliferation, MI was calculated in representative samples of each blood type were X-irradiated. The results showed that there was no significant difference among the cell cycle phases of lymphocytes in different blood types (P > 0.05). Similarly, both MI and NDI of lymphocytes derived from different blood types also did not show significant difference ( P > 0.05). The extensive interindividual variation within and among the blood types is likely responsible for the lack of significant difference in lymphocyte proliferation. Although spontaneous proliferation efficiency of lymphocytes of different blood types after PHA stimulation was grossly similar, the MI observed after radiation exposure showed a significant difference ( P < 0.05) indicating a differential proliferation response among the blood types. Our results suggest that the blood types did not have any impact on PHA-induced proliferation; however, a specific differential lymphocyte proliferation observed after radiation exposure needs to be considered.
Topics: Adult; Blood Group Antigens; Cell Cycle; Cell Nucleus Division; Cell Proliferation; Cells, Cultured; Female; Humans; Lymphocyte Activation; Lymphocytes; Male; Mitosis; Phytohemagglutinins; Young Adult
PubMed: 30320915
DOI: 10.1002/jcb.27858 -
Comparative Immunology, Microbiology... Sep 2023Feral birds residing close to urban settings exhibit higher immunocompetence against environmental pathogens than their counterparts in rural areas. In this study, we...
Feral birds residing close to urban settings exhibit higher immunocompetence against environmental pathogens than their counterparts in rural areas. In this study, we comprehensively evaluated the immunocompetence of five specific feral bird species and investigated the potential for interspecies transmission and pathogenicity of Avian orthoavulavirus-1 (AOAV-1) originating from the Anseriformes order. The immunocompetence assessment involved administering the phytohemagglutinin (PHA) test to individual groups of birds from rural and urban settings, measuring patagium thickness at specific time intervals (12, 24, 36, 48, and 60 h) following the administration of 0.1 mL (1 mg/mL) of PHA. Urban birds displayed significantly enhanced mean swelling responses, particularly urban pigeons, which exhibited a significant difference in patagium thickness at all-time intervals except for 24 h (p = 0.000, p = 0.12). Similarly, rural and urban quails and crows showed substantial differences in patagium thickness at all-time intervals except for 12 h (p = 0.542, p = 0.29). For the assessment of interspecies transmission potential and pathogenicity, each feral bird group was separately housed with naive broiler birds (n = 10 each) and challenged with a velogenic strain of AOAV-1 isolate (Mallard-II/UVAS/Pak/2016) at a dose of 1 mL (10 EID/mL). Urban birds demonstrated higher resistance to the virus compared to their rural counterparts. These findings highlight the specific immunocompetence of feral bird species and their potential contributions to AOAV-1 transmission and pathogenicity. Continuous monitoring, surveillance, and strict implementation of biosafety and biosecurity measures are crucial for effectively controlling AOAV-1 spillover to the environment and wild bird populations in resource-limited settings, particularly Pakistan.
Topics: Animals; Chickens; Animals, Wild; Newcastle disease virus; Ducks; Immunocompetence
PubMed: 37541170
DOI: 10.1016/j.cimid.2023.102036 -
Mediators of Inflammation 2018The pathogenesis of chronic venous disease (CVD) remains unclear, but lately inflammation is suggested to have an important role in its development. This study is aimed...
The pathogenesis of chronic venous disease (CVD) remains unclear, but lately inflammation is suggested to have an important role in its development. This study is aimed at assessing cytokines released by lymphocytes in patients with great saphenous vein (GSV) incompetence. In 34 patients exhibiting oscillatory flow (reflux) in GSV, blood was derived from the cubital vein and from the incompetent sapheno-femoral junction. In 12 healthy controls, blood was derived from the cubital vein. Lymphocyte culture with and without stimulation by phytohemagglutinin (PHA) was performed. Interleukins (IL) 1, 2, 4, 10, 12 (p70), and 17A; interleukin 1 receptor (IL-1ra); tumor necrosis factor- (TNF-); interferon-gamma (IFN-); and RANTES were assessed in culture supernatants by the Bio-Plex assay. In both stimulated and unstimulated samples, in the examined group, IL-1 and IFN- had higher concentrations and RANTES had lower concentrations when compared to those in the control group. In the examined group, IL-4 and IL-17A had higher concentrations without stimulation and TNF- had higher concentrations with stimulation. The GSV samples had higher IL-2, IL-4, IL-12 (p70), and IFN- concentrations without stimulation and lower IL-2 and TNF- concentrations with stimulation when compared to those of the upper limb in the examined group. These observations indicate that the oscillatory flow present in incompetent veins causes changes in the cytokine production by lymphocytes, promoting a proinflammatory profile. However, the relations between immunological cells, cytokines, and the endothelium require more insight.
Topics: Adult; Aged; Cytokines; Female; Healthy Volunteers; Humans; Immune System; Inflammation; Interferon-gamma; Lymphocytes; Male; Middle Aged; Oscillometry; Phytohemagglutinins; Saphenous Vein; Tumor Necrosis Factor-alpha; Young Adult
PubMed: 30013452
DOI: 10.1155/2018/7161346 -
Genes and Immunity Mar 2015Th1/Th17-type T-cell responses are upregulated in Behcet's disease (BD). However, signaling pathways associated with this aberrant immune response are not clarified....
Th1/Th17-type T-cell responses are upregulated in Behcet's disease (BD). However, signaling pathways associated with this aberrant immune response are not clarified. Whole-genome microarray profiling was performed with human U133 (Plus 2.0) chips using messenger RNA of isolated CD14(+) monocytes and CD4(+) T cells from peripheral blood mononucleated cell (PBMC) in patients with BD (n = 9) and healthy controls (HCs) (n = 9). Flow cytometric analysis of unstimulated (US) and stimulated (phytohaemagglutinin) signal transducer and activator of transcription (STAT3) and pSTAT3 expressions of PBMCs were also analyzed (BD and HC, both n = 26). Janus family of kinase (JAK1) was observed to be upregulated in both CD14(+) monocytes (1.95-fold) and CD4(+) T lymphocytes (1.40-fold) of BD patients. Using canonical pathway enrichment analysis, JAK/STAT signaling was identified as activated in both CD14(+) monocytes (P = 9.55E-03) and in CD4(+) lymphocytes (P =8.13E-04) in BD. Interferon signaling was also prominent among upregulated genes in CD14(+) monocytes (P = 5.62E-05). Glucocorticoid receptor signaling and interleukin (IL-6) signaling were among the most enriched pathways in differentially expressed genes in CD14+ monocytes (P = 2.45E-09 and 1.00E-06, respectively). Basal US total STAT3 expression was significantly higher in BD (1.2 vs 3.45, P < 0.05). The JAK1/STAT3 signaling pathway is activated in BD, possibly through the activation of Th1/Th17-type cytokines such as IL-2, interferon (IFN-γ), IL-6, IL-17 and IL-23.
Topics: Adult; Behcet Syndrome; CD4-Positive T-Lymphocytes; Female; Gene Expression Profiling; Genome-Wide Association Study; Humans; Interleukins; Janus Kinase 1; Lipopolysaccharide Receptors; Male; STAT3 Transcription Factor; Signal Transduction
PubMed: 25410656
DOI: 10.1038/gene.2014.64 -
Antimicrobial Agents and Chemotherapy Apr 2018In seeking substitutions for the current Chagas disease treatment, which has several relevant side effects, new therapeutic candidates have been extensively...
In seeking substitutions for the current Chagas disease treatment, which has several relevant side effects, new therapeutic candidates have been extensively investigated. In this context, a balanced interaction between mediators of the host immune response seems to be a key element for therapeutic success, as a proinflammatory microenvironment modulated by interleukin-10 (IL-10) is shown to be relevant to potentiate anti- drug activity. This study aimed to identify the potential immunomodulatory activities of the anti- K777, pyronaridine (PYR), and furazolidone (FUR) compounds in peripheral blood mononuclear cells (PBMC) from noninfected (NI) subjects and chronic Chagas disease (CD) patients. Our results showed low cytotoxicity to PBMC populations, with 50% cytotoxic concentrations (CC) of 71.0 μM (K777), 9.0 μM (PYR), and greater than 20 μM (FUR). In addition, K777 showed no impact on the exposure index (EI) of phytohemagglutinin-stimulated leukocytes (PHA), while PYR and FUR treatments induced increased EI of monocytes and T lymphocytes at late stages of apoptosis in NI subjects. Moreover, K777 induced a more prominent proinflammatory response (tumor necrosis factor alpha-positive [TNF-α] CD8/CD4, gamma interferon-positive [IFN-γ] CD4/CD8 modulated by interleukin-10-positive [IL-10] CD4 T/CD8 T) than did PYR (TNF-α CD8, IL-10 CD8) and FUR (TNF-α CD8, IL-10 CD8). Signature analysis of intracytoplasmic cytokines corroborated the proinflammatory/modulated (K777) and proinflammatory (PYR and FUR) profiles previously found. In conclusion, the lead compound K777 may induce beneficial changes in the immunological profile of patients presenting the chronic phase of Chagas disease and may contribute to a more effective therapy against the disease.
Topics: Apoptosis; Chagas Disease; Furazolidone; Immunologic Factors; Leukocytes; Naphthyridines; Phytohemagglutinins; Trypanosoma cruzi
PubMed: 29437629
DOI: 10.1128/AAC.01834-17 -
International Journal of Toxicology May 2016Information on the effects of phytoestrogens on animals has increased recently; however, there were only few studies on prenatal exposure on cellular immune response....
Information on the effects of phytoestrogens on animals has increased recently; however, there were only few studies on prenatal exposure on cellular immune response. Pregnant rats were assigned to 3 groups (12 rats per group), the first was fed control diet, the second was fed low-dose (6.5 g/100 g of diet) soy isoflavones, while the third was fed high-dose (26 g/100 g of diet) soy isoflavones. The female offspring cell-mediated immune response was determined using phytohemagglutinin (PHA) injection, and intumesce index was calculated on postnatal day 50. After 24 hours of PHA injection, blood samples were collected for tumor necrosis factor α, interferon γ (IFN-γ), and interleukin (IL)-12 determination. Spleen, thymus, and PHA-injected footpads were fixed for histopathology. Intumesce index was significantly (P < 0.05) reduced in rats' offspring born from dams fed low- and high-dietary soy isoflavones than that in control groups. Thymic relative weights in offspring of rats fed high-dietary soy isoflavones showed a significant (P < 0.05) decrease compared to that in the control group. Female offspring where low and high-dietary soy isoflavones were fed to their dams showed a significant (P < 0.05) decrease in IFN-γ and IL-12 than that in control ones. Spleen of rats born from dams fed high dose of dietary soy isoflavones showed lymphocytic depletion in white pulp. Taking together, it is clear that dietary soy isoflavones at prenatal period had immunosuppressive effect on female offspring after PHA stimulation. This effect was mediated through reduced IFN-γ that interplayed in IL-12 production pathway thus reducing its level.
Topics: Animals; Diet; Female; Immunosuppressive Agents; Interferon-gamma; Interleukin-12; Isoflavones; Leukocyte Count; Maternal-Fetal Exchange; Organ Size; Phytohemagglutinins; Pregnancy; Prenatal Exposure Delayed Effects; Rats, Wistar; Glycine max; Spleen; Thymus Gland; Tumor Necrosis Factor-alpha
PubMed: 26758869
DOI: 10.1177/1091581815625595 -
Frontiers in Immunology 2022Thermal injury induces concurrent inflammatory and immune dysfunction, which is associated with adverse clinical outcomes. However, these effects in the pediatric... (Observational Study)
Observational Study
Thermal injury induces concurrent inflammatory and immune dysfunction, which is associated with adverse clinical outcomes. However, these effects in the pediatric population are less studied and there is no standard method to identify those at risk for developing infections. Our goal was to better understand immune dysfunction and identify soluble protein markers following pediatric thermal injury. Further we wanted to determine which early inflammatory, soluble, or immune function markers are most predictive of the development of nosocomial infections (NI) after burn injury. We performed a prospective observational study at a single American Burn Association-verified Pediatric Burn Center. A total of 94 pediatric burn subjects were enrolled and twenty-three of those subjects developed a NI with a median time to diagnosis of 8 days. Whole blood samples, collected within the first 72 hours after injury, were used to compare various markers of inflammation, immune function, and soluble proteins between those who recovered without developing an infection and those who developed a NI after burn injury. Within the first three days of burn injury, innate and adaptive immune function markers (ex vivo lipopolysaccharide-induced tumor necrosis factor alpha production capacity, and ex vivo phytohemagglutinin-induced interleukin-10 production capacity, respectively) were decreased for those subjects who developed a subsequent NI. Further analysis of soluble protein targets associated with these pathways displayed significant increases in soluble CD27, BTLA, and TIM-3 for those who developed a NI. Our findings indicate that suppression of both the innate and adaptive immune function occurs concurrently within the first 72 hours following pediatric thermal injury. At the same time, subjects who developed NI have increased soluble protein biomarkers. Soluble CD27, BTLA, and TIM-3 were highly predictive of the development of subsequent infectious complications. This study identifies early soluble protein makers that are predictive of infection in pediatric burn subjects. These findings should inform future immunomodulatory therapeutic studies.
Topics: Biomarkers; CD27 Ligand; Child; Cross Infection; Hepatitis A Virus Cellular Receptor 2; Humans; Lipopolysaccharides; Phytohemagglutinins; Prospective Studies; Receptors, Immunologic
PubMed: 35958579
DOI: 10.3389/fimmu.2022.940835 -
The Journal of Comparative Neurology Apr 2019One of the main subcortical inputs to the basolateral nucleus of the amygdala (BL) originates from a group of dorsal thalamic nuclei located at or near the midline,...
One of the main subcortical inputs to the basolateral nucleus of the amygdala (BL) originates from a group of dorsal thalamic nuclei located at or near the midline, mainly from the central medial (CMT), and paraventricular (PVT) nuclei. Although similarities among the responsiveness of BL, CMT, and PVT neurons to emotionally arousing stimuli suggest that these thalamic inputs exert a significant influence over BL activity, little is known about the synaptic relationships that mediate these effects. Thus, the present study used Phaseolus vulgaris-leucoagglutinin (PHAL) anterograde tracing and electron microscopy to shed light on the ultrastructural properties and synaptic targets of CMT and PVT axon terminals in the rat BL. Virtually all PHAL-positive CMT and PVT axon terminals formed asymmetric synapses. Although CMT and PVT axon terminals generally contacted dendritic spines, a substantial number ended on dendritic shafts. To determine whether these dendritic shafts belonged to principal or local-circuit cells, calcium/calmodulin-dependent protein kinase II (CAMKIIα) immunoreactivity was used as a selective marker of principal BL neurons. In most cases, dendritic shafts postsynaptic to PHAL-labeled CMT and PVT terminals were immunopositive for CaMKIIα. Overall, these results suggest that CMT and PVT inputs mostly target principal BL neurons such that when CMT or PVT neurons fire, little feed-forward inhibition counters their excitatory influence over principal cells. These results are consistent with the possibility that CMT and PVT inputs constitute major determinants of BL activity.
Topics: Amygdala; Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Dendrites; Male; Midline Thalamic Nuclei; Neuronal Tract-Tracers; Phytohemagglutinins; Rats, Sprague-Dawley; Synapses
PubMed: 30311651
DOI: 10.1002/cne.24557 -
Journal of Tissue Engineering and... Mar 2022Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) can promote osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMMSCs), and CTLA4-modified bone...
Demineralized bone matrix combined with cytotoxic T-lymphocyte-associated protein 4 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells and suppresses the activation of T lymphocytes in vitro.
Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) can promote osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMMSCs), and CTLA4-modified bone marrow mesenchymal stem cells possess immunoregulatory effects. In the present study, we aimed to construct a new tissue engineering bone using demineralized bone matrix and CTLA4 protein, designated as DBM-CTLA4 (+). The effects of DBM-CTLA4 (+) on the osteogenic differentiation of hBMMSCs and T lymphocyte activation were evaluated through in vitro experiments. The cumulative release of CTLA4 from DBM-CTLA4 (+) was determined using enzyme-linked immunosorbent assay. DBM-CTLA4 (+) was co-cultured in a Transwell chamber with either phytohemagglutinin-treated hBMMSCs or human peripheral blood mononuclear cells (hPBMCs). Osteogenic differentiation of hBMMSCs was assessed by calcium deposition, ALP activity, and the protein levels of COL1A1, RUNX2, BMP2, and OPN. T lymphocyte activity was assessed by measuring the protein levels of IL-2, L-17, HLA-DRA1, IFN-γ, and RANKL. Our results showed that the cumulative release rates of CTLA4 at 7, 14, 21, and 28 days were 12.6% ± 1.4%, 30.2% ± 2.3%, 49.8% ± 3.8%, and 60.5% ± 2.7%, respectively. Compared to the negative control, DBM-CTLA4 (+) promoted the proliferation of hBMMSCs, and enhanced calcium deposition, ALP activity, and protein levels of COL1A1, RUNX2, BMP2, and OPN. Moreover, DBM-CTLA4 (+) decreased the levels of IL-2, IL-17, HLA-DR, IFN-γ, and RANKL in hPBMCs treated with phytohemagglutinin. In conclusion, DBM-CTLA4 (+) promoted proliferation and osteogenic differentiation of hBMMSCs and suppressed T lymphocyte activation.
Topics: Bone Marrow Cells; Bone Matrix; CTLA-4 Antigen; Calcium; Cell Differentiation; Cells, Cultured; Core Binding Factor Alpha 1 Subunit; Humans; Interleukin-2; Leukocytes, Mononuclear; Mesenchymal Stem Cells; Osteogenesis; Phytohemagglutinins; T-Lymphocytes, Cytotoxic
PubMed: 34965018
DOI: 10.1002/term.3281