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Cytokine Production (cytokine + production)
Kinds of Cytokine Production Terms modified by Cytokine Production Selected AbstractsEffects of Ethanol on Cytokine Production After Surgery in a Murine Model of Gram-Negative PneumoniaALCOHOLISM, Issue 2 2008Claudia D. Spies Background:, Both alcohol abuse and surgery have been shown to impair immune function. The frequency of postoperative infectious complications is 2- to 5-fold increased in long-term alcoholic patients, leading to prolonged hospital stay. Following surgery, an increase in interleukin (IL)-6 has been shown to be associated with increased tissue injury and interleukin 1-(IL-10) is known to represent an anti-inflammatory signal. The purpose of this study was to test the hypothesis that several days of excess alcohol consumption results in more pronounced immunosuppression. We assume that alcoholic animals show increased levels of IL-10 in response to infection and increased IL-6 due to a more pronounced lung pathology. Methods:, Thirty-two female Balb/c mice were pretreated with ethanol (EtOH) at a dose of (3.8 mg/g body weight) or saline (NaCl) for 8 days. At day 8 of the experiment all mice underwent a median laparotomy. Two days postsurgery mice were either applicated 104 CFU Klebsiella pneumoniae or received sham-infection with saline. A total number of 4 groups (EtOH/K. pneumoniae; NaCl/K. pneumoniae; EtOH/Sham-infection, NaCl/Sham-infection) was investigated and a clinical score evaluated. Twenty-four hours later mice were killed; lung, spleen, and liver were excised for protein isolation and histological assessment. IL-6 and IL-10 levels were detected by ELISA. Results:, Alcohol-exposed mice exhibited a worsened clinical appearance. The histological assessment demonstrated a distinct deterioration of the pulmonary structure in alcohol-treated animals. In the lung, IL-6 and IL-10 was significantly increased in alcohol-exposed infected mice compared to saline-treated infected mice. The clinical score correlated significantly with IL-6 (r = 0.71; p < 0.01) and IL-10 levels (r = 0.64; p < 0.01) in the lung. Conclusions:, Ethanol treatment in this surgical model led to a more severe pulmonary infection with K. pneumoniae which was associated with more tissue destruction and increased levels of IL-6 and IL-10 and a worsened clinical score. [source] Phagocytosis of Apoptotic Trophoblast Cells by Human Endometrial Endothelial Cells Induces Proinflammatory Cytokine ProductionAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010Bing Peng Citation Peng B, Koga K, Cardenas I, Aldo P, Mor G. Phagocytosis of apoptotic trophoblast cells by human endometrial endothelial cells induces proinflammatory cytokine production. Am J Reprod Immunol 2010; 64: 12,19 Problem, Apoptosis is a normal constituent of trophoblast turnover in the placenta; however in some cases, this process is related to pregnancy complications such as preeclampsia. Recognition and engulfment of these apoptotic trophoblast cells is important for clearance of dying cells. The aim of this study was to show the cross talk between human endometrial endothelial cells (HEECs) and apoptotic trophoblast cells in an in vitro coculture model and its effect on cytokine production by HEECs. Method of study, Fluorescent-labeled HEECs were cocultured with fluorescent-labeled apoptotic human trophoblast cells. Confocal microscopy and flowcytometry were used to show the interaction between these two types of cells. Cytokine profiles were determined using multiplex analysis. Results, HEECs are capable to phagocytose apoptotic trophoblasts. This activity is inhibited by the phagocytosis inhibitor cytochalasin B. Phagocytosis of apoptotic trophoblast cells induced the secretion of the proinflammatory cytokines interleukin-6 and monocyte chemoattractant protein-1 by HEECs. Conclusion, This study provides the first evidence that HEECs have an ability to phagocytose apoptotic trophoblasts. Furthermore, we demonstrated an inflammatory response of HEECs after phagocytosing the apoptotic trophoblast cells. This event may contribute to the inflammatory response in both normal pregnancy and pathologic pregnancy such as preeclampsia. [source] ORIGINAL ARTICLE: Characterization of Cytokine Production by Human Term Placenta Macrophages In VitroAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2008Oleg Pavlov Problem, Macrophages are apparently the only immune cells within placenta villi, yet functions of these cells remain obscure. It has been postulated that placental macrophages accomplish regulatory roles at the fetal,maternal interface by means of wide variety of secreted cytokines. We attempt to analyze the patterns of cytokine production in an isolated population of placental macrophages. Method of study, Macrophages were obtained from term placentas in the absence of spontaneous labor. The basal and lipopolysaccharide (LPS)-stimulated levels of intracellular cytokines were detected by flow cytometry. The basal cytokine secretion was determined by BDÔCytometry Bead Array (BD Biosciences, San Diego, CA, USA). Results, Intracellular IL-1,, IL-1,, IL-6, and TNF, were detected in 31, 27, 4, and 3% CD68+ cells, respectively. Stimulation with LPS increased the proportions of cytokine-producing CD68+ cells to 48, 50, 28, and 49%, respectively. Under basal conditions, levels of released TNF, and IL-6, respectively, were 20- and 25-fold higher when compared with IL-1, while IL-10 was secreted in small but detectable amounts. When a secretory activity was estimated for cytokine-producing cells, the secretion rate for TNF, and IL-6 overwhelmingly surpassed that for IL-1, (TNF,:IL-6:IL-1, ratio was 192:145:1). Conclusion, These results suggest functional heterogeneity of the placental macrophage population and contribute to the elucidation of regulatory roles of these cells in gestation. [source] Changes in Cytokine Production During and After Normal PregnancyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2000YUKI SHIMAOKA PROBLEM: The systemic T helper 1/T helper 2 (Th1/Th2) cytokine balance during normal human pregnancy is controversial, and observations about the balance in the postpartum period have only been reported for up to 3 months. METHOD: Whole-blood, from 83 healthy pregnant women, 80 healthy postpartum women, and 31 healthy non-pregnant women was stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, and the levels of cytokines in the supernatant were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The production of all measured cytokines decreased during pregnancy, especially in the second trimester. After delivery, interferon-, (IFN-,) and interleukin-2 (IL-2) increased from 2 to 11 months postpartum, and IL-4 increased from 6 to 11 months postpartum. CONCLUSIONS: These data indicate that 1) decreases in production of both Th1- and Th2-type cytokines during pregnancy may be related to the pregnancy-induced amelioration of autoimmune diseases; 2) increases in production of both Th1- and Th2-type cytokines in the postpartum period may be related to the postpartum aggravation of autoimmune diseases. [source] Alteration of Cytokine Production in Follicular Cystic Ovaries Induced in Mice by Neonatal Estradiol InjectionAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2000ROHINI R. DESHPANDE PROBLEM: Neonatal estradiol injections in mice lead to follicular cystic ovaries that are similar to ovaries in patients with polycystic ovarian syndrome (PCOS). The present study examined ovarian cytokine production following neonatal estradiol injection. METHOD OF STUDY: Female (C3H/HeJ×129/HeJ)F1 mice were injected daily with 20 ,g 17,-estradiol from 0,3 days postpartum. At intervals, animals were sacrificed to determine ovarian architecture, circulating levels of estradiol, ovarian and peritoneal machrophage cytokine production, and ovarian P450 aromatase enzyme mRNA levels. RESULTS: Similar to PCOS, our results show that neonatally estradiol-injected mice have lower levels of circulating estrogen that are correlated with decreased mRNA levels of P450 aromatase enzyme. Our data also show that follicular cystic ovaries have increased tumor necrosis factor (TNF)-, and interleukin (IL)-6 production. This increase in TNF-, and IL-6 production is also observed in peritoneal macrophages of estradiol-injected mice. CONCLUSION: The present study showed that neonatal estrogen injection in mice has an overall systemic effect on cytokine production. We speculate that increased cytokine production may alter certain important steps in follicular maturation, ultimately contributing to ovarian dysfunction. [source] Stimulation of Uterine Cell Cytokine Production By Ovarian HormonesAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2000J.A. DELOIA PROBLEM: Although leukocytes do not possess significant numbers of ovarian steroid hormone receptors, their numbers in the endometrium vary consistently, relative to the menstrual cycle. The possibility that cell types within the endometrium express leukocyte-attracting genes in response to ovarian hormones was investigated. METHOD OF STUDY: Endometrial biopsies were collected 10 days post-leutinizing hormone surge; the cell types were separated and cultured individually for 5 days in the presence of increasing amounts of estrogen or progesterone. Following culture, RNA was collected from cells and reverse-transcription-polymerase chain reaction was used to determine relative levels of gene expression of monocyte chemotactic proteins (MCP)-1, -2, and -3, and interleukin (IL)-12p35 and p40. RESULTS: Although both endometrial stroma and glands were able to make MCP mRNA, steady-state levels of gene expression did not vary significantly relative to hormone treatment. The same was found for the p35 molecule of the IL-12 gene; however, differences were observed for the p40 subunit. CONCLUSIONS: Within the human endometrium, chemokines other than MCP and IL-12 are most likely responsible for cycle-related leukocyte recruitment. [source] Release of (1,3)-,-D-Glucan from Depth-type Membrane Filters and Their In Vitro Effects on Proinflammatory Cytokine ProductionARTIFICIAL ORGANS, Issue 8 2003Atsushi Ohata Abstract:, To clarify the origin of (1,3)-,-D-glucan in blood products and assess the biological activity of filter extracts, we evaluated (1,3)-,-D-glucan extraction from depth filters used to process blood products and their in vitro effects on proinflammatory cytokine production from macrophages. Cellulose or nylon filters were analyzed for (1,3)-,-D-glucan using the Fungitec G test. To evaluate the biological activity of the filter extracts, Mono Mac 6 cells (a human macrophage cell line) were cultured with filter extracts with or without lipopolysaccharide, and tumor necrosis factor-alpha (TNF-,) and interleukin-1 beta (IL-1,) concentrations in the culture media were measured. (1,3)-,-D-Glucan was released from seven cellulose filters but the nylon filter level was undetectable. Proinflammatory cytokine production ranged from 74.3% to 119.0% of the control for TNF-, and 81.2% to 115.9% for IL-1,. TNF-, and IL-1, levels were low without lipopolysaccharide. The data indicate that (1,3)-,-D-glucan in blood products is contaminated with the depth filters and that these filter extracts modulate proinflammatory cytokine production from macrophages. [source] Immunomodulatory effects of probiotic bacteria DNA: IL-1 and IL-10 response in human peripheral blood mononuclear cellsFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2003Karen Manon Lammers Abstract A new therapeutic approach for inflammatory bowel diseases is based on the administration of probiotic bacteria. Prokaryotic DNA contains unmethylated CpG motifs which can activate immune responses, but it is unknown whether bacterial DNA is involved in the beneficial effects obtained by probiotic treatment. Peripheral blood mononuclear cells (PBMC) from healthy donors were incubated with pure DNA of eight probiotic strains and with total bacterial DNA from human feces collected before and after probiotic ingestion. Cytokine production was analyzed in culture supernatants. Modification of human microflora after probiotic administration was proven by polymerase chain reaction analysis. Here we show that Bifidobacterium genomic DNA induced secretion of the antiinflammatory interleukin-10 by PBMC. Total bacterial DNA from feces collected after probiotic administration modulated the immune response by a decrease of interleukin-1, and an increase of interleukin-10. [source] Induction of potent cellular immune response in mice by hepatitis C virus NS3 protein with double-stranded RNAIMMUNOLOGY, Issue 1 2007Bo Jin Summary Double-stranded RNA is produced during virus replication and, together with the viral antigen, is responsible for inducing host antivirus immunity. The hepatitis C virus (HCV) non-structural protein-3 (NS3) has been implicated in the immune evasion of HCV, and is one of the prime targets for inducing immunity against HCV infection. Mice were immunized with recombinant NS3 protein (rNS3) and poly (I:C) emulsified in Montanide ISA 720 (M720). Cytokine production was assayed by enzyme-linked immunospot assay, and CD4+ IFN-,+ T helper (Th) cells or CD8+ IFN-,+ cytotoxic T lymphocytes were detected by flow cytometry. Anti-NS3 titre and immunoglobulin G2a (IgG2a) and IgG1 levels were monitored by enzyme-linked immunosorbent assay. Administration of rNS3 formulated in poly (I:C) and M720 induced anti-NS3 titres with a predominantly IgG2a isotype comparable to those induced by rNS3 in CpG-ODN and M720. The cytokine profiles showed that this formulation induced a Th1-biased immune response with several-fold more interferon-, (IFN-,)-producing cells than interleukin-4-producing cells. In contrast, rNS3 in M720 induced a Th2-biased immune response. The frequency of IFN-,-producing CD4+ and CD8+ cells induced by rNS3 in poly (I:C) and M720 was significantly higher than that induced by rNS3, rNS3 in M720, or rNS3 in poly (I:C), and was comparable to that induced by rNS3 in CpG-ODN with M720. The antigen-specific CD8+ T-cell immune response persisted for up to 7 months after immunization. In conclusion, poly (I:C) with rNS3 in M720 can elicit a strong and persistent Th1-biased immune response and a cytotoxic T-lymphocyte response through cross-priming in mice. This study highlighted a promising formulation for inducing an efficient cellular immune response against HCV that has potential for HCV vaccine development. [source] Impact of elemental diet on mucosal inflammation in patients with active Crohn's disease: Cytokine production and endoscopic and histological findingsINFLAMMATORY BOWEL DISEASES, Issue 6 2005Takayuki Yamamoto MD Abstract Background: The aim of this study was to examine the impact of elemental diet on mucosal inflammation in Crohn's disease (CD), mainly by cytokine measurements. Methods: Twenty-eight consecutive patients with active CD were treated with an elemental diet (Elental) for 4 weeks. The mucosal biopsies were obtained from the terminal ileum and large bowel before and after treatment. As a control group, mucosal biopsies were obtained from 20 patients without inflammation. Mucosal cytokine concentrations were measured by enzyme-linked immunosorbent assay. Results: After treatment, clinical remission was achieved in 20 patients (71%). Endoscopic healing and improvement rates were 44% and 76% in the terminal ileum and 39% and 78% in the large bowel, respectively. Histologic healing and improvement rates were 19% and 54% in the terminal ileum and 20% and 55% in the large bowel, respectively. Before treatment, the mucosal concentrations of interleukin (IL)-1,, IL-1 receptor antagonist (IL-1ra), IL-6, IL-8, and tumor necrosis factor-, in the ileum and large bowel were significantly higher than in controls. These cytokine concentrations decreased to the levels of control after treatment. IL-1ra/IL-1, ratio in the ileum and large bowel was significantly lower than in controls before treatment. The ratio increased to the level of controls after treatment. The endoscopic and histologic healing of the mucosal inflammation was associated with a decline of the mucosal cytokines and an increase of the IL-1ra/IL-1, ratio. Conclusions: The elemental diet (Elental) reduced mucosal cytokine production and corrected an imbalance between proinflammatory and anti-inflammatory cytokines in CD. [source] APOE epsilon-4 allele and cytokine production in Alzheimer's diseaseINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 4 2010Paolo Olgiati Abstract Objective The APOE epsilon-4 allele has consistently emerged as a susceptibility factor for Alzheimer's disease (AD). Pro-inflammatory cytokines are detectable at abnormal levels in AD, and are thought to play a pathophysiological role. Animal studies have shown dose-dependent correlations between the number of APOE epsilon-4 alleles and the levels of pro-inflammatory cytokines. The aims of this study were to investigate the influence of APOE genotypes on TNF- ,, IL-6, and IL-1, secreted by peripheral blood mononuclear cells (PBMC) from human patients with AD and to analyze the correlation between cytokine production and AD clinical features. Methods Outpatients with AD (n,=,40) were clinically evaluated for cognitive decline (MMSE) and psychiatric symptoms (Cornell Scale for Depression in Dementia; Neuropsychiatric Inventory) and genotyped for APOE variants. PBMCs were isolated from the donors and used to assess spontaneous and PMA-stimulated secretion of TNF- ,, IL-6, and IL-1,. Cytokine production was determined by immuno-enzymatic assays (ELISA). Results In comparison with their counterparts without APOE4, patients with at least one copy of the APOE epsilon-4 allele showed higher spontaneous (p,=,0.037) and PMA-induced (p,=,0.039) production of IL-1, after controlling for clinical variables. Significant correlations were reported between NPI scores (psychotic symptoms) and IL-6 production. Conclusion These preliminary findings suggest the involvement of inflammatory response in the pathogenic effect of the APOE epsilon-4 allele in AD, although their replication in larger samples is mandatory. The modest correlations between pro-inflammatory cytokines released at peripheral level and AD features emphasizes the need for further research to elucidate the role of neuroinflammation in pathophysiology of AD. Copyright © 2009 John Wiley & Sons, Ltd. [source] Cytokine production from sputum cells and blood leukocytes in asthmatics according to disease severityALLERGY, Issue 7 2010M. Manise To cite this article: Manise M, Schleich F, Gusbin N, Godinas L, Henket M, Antoine N, Corhay JL, Louis R. Cytokine production from sputum cells and blood leukocytes in asthmatics according to disease severity. Allergy 2010; 65: 889,896. Abstract Background:, Although mild to moderate asthma is known to be Th2 driven, cytokines produced in refractory asthma might not fit the classical Th2 pattern. Methods:, The aim of our study was to assess the cytokine production by sputum and blood cells from 15 refractory asthmatics (American Thoracic Society Criteria) compared to 15 mild untreated and 17 moderate treated asthmatics and 22 healthy subjects. Spontaneous production of interleukin (IL)-4, IL-6, IL-10, interferon-,, and tumor necrosis factor , was measured by immunotrapping after 24 h sputum or blood cell culture. Results:, Moderate and refractory asthmatics were both characterized by a lower production of IL-6 from their airway cells compared to healthy subjects. However, the difference was no longer significant when expressing the results per gram of sputum. No significant difference between the three groups was found regarding other cytokines. As for cytokine production from blood, the three groups of asthmatics exhibited raised production of IL-4 when compared to healthy subjects, and this was true when results were expressed per blood volume or after normalization for total leukocyte cell count. Moderate asthmatics exhibited greater production of IL-10 when compared to refractory asthmatics and healthy subjects when results were normalized for total leukocyte cell count. Conclusions:, Sputum cells from moderate and refractory asthmatics release less IL-6. While the systemic overproduction of IL-4 was observed through the all spectrum of asthma severity, moderate asthmatics exhibited greater systemic IL-10 production compared to refractory asthmatics. [source] Counter regulation of the high affinity IgE receptor, Fc,RI, on human airway dendritic cells by IL-4 and IL-10ALLERGY, Issue 11 2009A. Faith Background:, Immunoglobulin E is a signalling molecule within the environment of the respiratory tract, the high affinity receptor for which, Fc,RI, is expressed by dendritic cells (DC). Little is known, however, of the expression and function of Fc,RI on DC in the human respiratory tract. Methods:, CD1c+ DC were purified from surgically resected nasal turbinates of 11 atopic and 12 nonatopic patients with chronic rhinosinusitis. Expression of Fc,RI was determined by flow cytometry. Cytokine production by DC was determined by cytometric bead array. Results:, Expression of Fc,RI was significantly elevated on respiratory tract dendritic cells (RTDC) from atopic as compared to nonatopic patients. Activation of RTDC through Fc,RI induced production of the pro-inflammatory cytokines IL-6 and TNF-,, and the anti-inflammatory cytokine IL-10. The production of IL-6 and TNF-, was elevated in atopic compared to nonatopic patients studied. Conversely IL-10 production was elevated in nonatopic patients. Concomitant activation of Fc,RI and stimulation of RTDC with IL-4 inhibited production of IL-10 by RTDC. Neutralization experiments with anti-IL-10 Ab enhanced whereas addition of exogenous IL-10 to RTDC inhibited Fc,RI-mediated inflammatory cytokine production. Conclusion:, The function of Fc,RI on RTDC from patients with rhinosinusitis is susceptible to counter regulation by IL-4 and IL-10. [source] Effects of Bifidobacterium bifidum on adaptive immune senescence in aging miceMICROBIOLOGY AND IMMUNOLOGY, Issue 10 2010Yu-Rong Fu ABSTRACT Bifidobacteria are a natural component of the bacterial flora of the human body and have a symbiotic bacteria-host relationship with human beings. Aging is associated with reduced numbers of beneficial colonic Bifidobacteria and impaired immunity. The possible anti-senescence effects of Bifidobacteria are presently unknown. The aims of the present study were to investigate possible anti-senescence effects of B. bifidum on naturally senescent mice and to explore their mechanisms. After treatment with B. bifidum, mice were killed and samples collected. Cytokine production in serum and lymphocyte culture supernatant, anti-oxidation activity and gene expression were measured. B. bifidum significantly increased cytokine IL-2 and IFN-, levels but decreased proinflammatory cytokines IL-6 and TNF-, concentrations. Moreover, B. bifidum improved anti-oxidation activity and reduced lipid peroxidation in thymus and spleen. In addition, B. bifidum down-regulated p16 expression in thymus and spleen. Taken together, the results indicate, for the first time, that B. bifidum delays senescence by several mechanisms, including enhancement of anti-oxidation activity in thymus and spleen, alteration of gene expression and improvement in immune function. [source] T lymphocytes expressing CCR3 are increased in allergic rhinitis compared with non-allergic controls and following allergen immunotherapyALLERGY, Issue 1 2007J. N. Francis Background:, In T cell-associated allergic inflammation, homing of T-helper 2 (Th2) effector cells to mucosal sites may be influenced by chemokine receptor expression. Previous studies have identified CCR3 and CCR4 as putative markers of Th2 cells and CCR5 and CXCR3 as markers of Th1 cells. The aim of this study was to assess differential chemokine receptor expression from symptomatic atopic grass pollen-sensitive subjects, compared with patients on high-dose allergen injection immunotherapy (IT) and healthy controls. Methods:, We examined chemokine receptor expression (CCR1,7 and CXCR1,4) by flow cytometry of peripheral blood CD4+ and CD8+ T cells. We also depleted peripheral blood mononuclear cell (PBMC) populations of CCR3+ CD4+ cells by magnetic bead separation and cells were stimulated with grass pollen allergen for 6 days. Cytokine production was measured by enzyme-linked immunosorbent assay. Results:, On freshly isolated PBMC, atopic individuals exhibited increased numbers of CCR3+ CD4+ cells compared with normal controls (P < 0.01). CCR3 expression in IT patients was reduced compared with matched atopic rhinitic controls (P < 0.05) and comparable with that observed in normal subjects. Depletion of CCR3+ CD4+ cells from allergen-stimulated PBMC cultures resulted in decreased interleukin (IL)-5 production compared with whole CD4+ populations (P < 0.05). Freshly isolated CCR3+ CD4+ cells have significantly higher intracellular IL-4 and lower IFN- , levels than CCR3, CD4+ cells. CD4+ T cells cultured from both peripheral cells and nasal biopsies demonstrated increased expression of CCR3 in the presence of IL-4 (P < 0.05). Conclusion:, CCR3+ CD4+ T cells are increased in allergic rhinitis, are reduced by allergen IT, have a Th2 phenotype and contribute to allergen-specific responses. Strategies against CCR3+ T cells may be effective in human allergic diseases. [source] Cytokine production in response to endodontic infection in germ-free miceMOLECULAR ORAL MICROBIOLOGY, Issue 6 2002A. P. Ribeiro Sobrinho This study evaluated the cytokine profiles (type 1 or type 2) that are triggered by and modulate endodontic periapical infections in the root canal system of germ-free mice. Microorganisms isolated from two patients with pulpal necrosis were inoculated into two groups of experimental animals: group I (Gemella morbillorum) and group II (Bifidobacterium adolescentis, Fusobacterium nucleatum and Clostridium butyricum). In vitro, G. morbillorum induced type 1 cytokine synthesis, while the modulation processed in vivo seemed to have the opposite effect, with a reduction in the basal levels of IL-12 and IFN-,, IL-4-independent down-modulation. In vitro, microorganisms from group II, in poly-infection, induced a reduction of type 1 cytokine levels from day 10 to day 20, which seemed to be modulated via IL-4. In vivo, however, a predominance of the immune response to one species over the others occurred. [source] Regulation of immune responses to Strongyloides venezuelensis challenge after primary infection with different larvae dosesPARASITE IMMUNOLOGY, Issue 3 2010H. C. SCHILTER Summary Nematode infections are generally followed by high rates of reinfection, leading to elevated prevalence in endemic areas. Therefore, the effective control of nematode infections depends on understanding the induction and regulation of protective mechanisms. However, most experimental models for protective immune response against nematodes use high parasite exposure, not always reflecting what occurs naturally in human populations. In this study, we tested whether infecting mice with different Strongyloides venezuelensis larvae loads would affect protective responses against reinfection. Interestingly, we found that a previous infection with 10,500 larvae conferred high rate of protection against reinfection with S. venezuelensis in mice, by destroying large numbers of migrating larvae. However, low-dose priming did not abolish adult worm maturation, as detected in high-dose primed group. Results also indicated that a previous low-dose infection delayed the development of cellular infiltrate, while a high inoculum rapidly induced these inflammatory features. Cytokine production by splenocyte cultures of challenge infected mice demonstrated that low-dose priming had increased production of IL-4 and IFN-,, while high-dose induced IL-4 production but not IFN-,. Our data support the hypothesis that low-dose nematode infection does not induce a polarized type-2 immune response, allowing adult worm survival. [source] Viral ssRNA Induces First Trimester Trophoblast Apoptosis through an Inflammatory MechanismAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010Paulomi B. Aldo Citation Aldo PB, Mulla MJ, Romero R, Mor G, Abrahams VM. Viral ssRNA induces first-trimester trophoblast apoptosis through an inflammatory mechanism. Am J Reprod Immunol 2010; 64: 27,37 Problem, Infection during pregnancy represents a significant cause of mobility and mortality. While viruses pose a major threat, little is known about their effect on early pregnancy, or the mechanisms involved. The objective of this study was to characterize the trophoblast response following exposure to viral ssRNA. Method of study, First trimester trophoblast cells were treated with or without viral ssRNA. Cytokine production was measured using multiplex analysis and ELISA. Apoptosis was determined using Hoechst staining, cell viability, and caspase activity assays. Results, Treatment of trophoblasts with viral ssRNA increased their secretion of IL-8, IL-6, and IFN,. However, the ssRNA also induced trophoblast apoptosis. To test whether the viral ssRNA-induced inflammatory response was responsible for this induction of apoptosis, conditioned media (CM) from trophoblasts were added to a fresh culture of cells. The CM from viral ssRNA-treated induced higher levels of trophoblast apoptosis than the control CM. Moreover, recombinant IFN, induced trophoblast apoptosis. Conclusion, We demonstrate that viral ssRNA induces a pro-inflammatory and type I interferon response in the trophoblast and this inflammatory process may indirectly induce trophoblast apoptosis. These results provide a novel mechanism by which certain viral infections might compromise placental integrity and function, and therefore, pregnancy outcome. [source] Pregnancy-Specific Glycoproteins Function as Immunomodulators by Inducing Secretion of IL-10, IL-6 and TGF-,1 by Human MonocytesAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2001SARA K. SNYDER PROBLEM: Low levels of pregnancy-specific glycoproteins (PSGs) in maternal serum have been correlated with complications of pregnancy. We investigated the ability of human PSGs to regulate in vitro production of cytokines. METHOD OF STUDY: Human monocytes and murine RAW 264.7 cells were treated with recombinant PSG1, PSG6, PSG11, or a truncated PSG6 consisting of only the N-terminal domain (PSG6N). Cytokine production in response to PSG-treatment was measured by ELISA and/or reverse transcriptase-PCR. RESULTS: All PSGs tested induced secretion of interleukin (IL)-10, IL-6 and transforming growth factor (TGF)-,1 by both human and murine cells, but not IL-1,, tumor necrosis factor (TNF)-, or IL-12. The N-terminal domain of PSG6 was sufficient for induction of monocyte cytokine secretion. Induction of IL-10 and IL-6 was preceded by an increase in the specific mRNAs. CONCLUSIONS: PSG1, PSG6, PSG6N, and PSG11 induce dose-dependent secretion of anti-inflammatory cytokines by human monocytes. Human and murine PSGs exhibit cross-species activity. Our results are consistent with a role for PSGs in modulation of the innate immune system. [source] Role of CD8+ CD25+ Foxp3+ regulatory T cells in multiple sclerosisANNALS OF NEUROLOGY, Issue 5 2010Jorge Correale MD Objective The objective of this study was to investigate the role of CD8+ CD25+ FoxP3+ cells during the course of multiple sclerosis (MS). Methods Peripheral blood and cerebrospinal fluid (CSF) CD8+ T-cell clones (TCCs) recognizing autoreactive CD4+ T cells were isolated from 20 MS patients during exacerbations, 15 patients in remission, 15 healthy subjects, and 10 patients with other inflammatory neurological diseases. Characteristics of noncytotoxic CD8+ CD25+ regulatory T cells were studied. Cell phenotype was evaluated using flow cytometry. Cytokine production and phospho-signal transducer and activator of transcription 3 (STAT3) concentration were determined using enzyme-linked immunosorbent assay. To assess 2,3-dioxygenase (IDO) activity on dendritic cells (DCs), kynurenine concentration was measured by high-performance liquid chromatography. Results Inhibition of CD4+ self-reactive T-cell proliferation, and of interferon-, and interleukin (IL)-17 secretion, was observed after adding CD8+ CD25+ FoxP3+ cells to cultures. Suppression was abrogated by silencing FoxP3 using small interfering RNA. Cells were CD122+, CTLA-4+, GITR+, CCR7+, and CD62L+, producing IL-10 and transforming growth factor-,. CD8+ CD25+ FoxP3+ cells downregulated costimulatory molecule expression on dendritic cells through a STAT3-mediated pathway, resulting in less efficient antigen presentation, and induced IDO expression on DCs through STAT3 and cytotoxic T-lymphocyte antigen 4-dependent mechanisms. CD8+ regulatory TCC cloning frequency studied in blood and CSF was suppressed to a greater degree during exacerbations than during remission or in controls. Likewise, in CSF of MS patients during acute exacerbations, lower levels of CD8+ CD25+ FoxP3+ T cells were detected using flow cytometry. Interpretation CD8+ CD25+ FoxP3+ cells are novel regulatory cells exerting significant influence over self-reactive CD4+ T-cell regulation during the course of MS. Induction of these cells may provide new therapeutic alternatives for MS by eliminating or inhibiting self-reactive T cells. ANN NEUROL 2010;67:625,638 [source] Depletion of functionally active CD20+ T cells by rituximab treatmentARTHRITIS & RHEUMATISM, Issue 12 2009Esther Wilk Objective Rituximab is a therapeutic anti-CD20 antibody used for in vivo depletion of B cells in proliferative and autoimmune diseases. However, the mechanisms of action are not fully understood, since not all of the therapy-mediated effects can be explained by the depletion of antibody-secreting cells. In addition to B cells, there is also a small population of T cells coexpressing CD20 in all individuals. This study was conducted to examine the phenotype and function of CD3+CD20+ T cells in patients with rheumatoid arthritis (RA) and healthy controls. Methods The phenotype and apoptosis of peripheral blood mononuclear cells from healthy donors and RA patients were examined by 4-color fluorescence-activated cell sorting analyses. Cytokine production was determined by intracellular staining and measurement of cytokines in the supernatants. Proliferation of sorted T cell populations was analyzed using 3H-thymidine uptake assays. Results In healthy individuals, 0.1,6.8% of peripheral blood T cells (mean 1.6%; n = 142) coexpressed CD20, which was not significantly different from that in the peripheral blood of RA patients, in whom 0.4,2.6% of T cells (mean 1.2%; n = 27) were CD20+. During rituximab therapy, the CD20+ T cells along with the B cells were eliminated from the RA peripheral blood. Among the CD20+ T cells, 45% coexpressed CD8 and 55% coexpressed CD4. Polyclonal CD3+CD20+ cells were functionally characterized by constitutive cytokine production (i.e., interleukin-1, and tumor necrosis factor ,), a low proliferative capacity, a high activation state, and enhanced susceptibility to apoptosis. Conclusion These findings suggest that CD20+ T cells represent a terminally differentiated cell type with immune-regulatory and proinflammatory capacities. Depletion of CD20+ T cells may be an additional mechanism by which anti-CD20 therapy functions in patients with RA. [source] Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritidesARTHRITIS & RHEUMATISM, Issue 8 2008Camilla Jandus Objective A distinct subset of proinflammatory CD4+ T cells that produce interleukin-17 was recently identified. These cells are implicated in different autoimmune disease models, such as experimental autoimmune encephalomyelitis and collagen-induced arthritis, but their involvement in human autoimmune disease has not yet been clearly established. The purpose of this study was to assess the frequency and functional properties of Th17 cells in healthy donors and in patients with different autoimmune diseases. Methods Peripheral blood was obtained from 10 psoriatic arthritis (PsA), 10 ankylosing spondylitis (AS), 10 rheumatoid arthritis (RA), and 5 vitiligo patients, as well as from 25 healthy donors. Synovial tissue samples from a separate group of patients were also evaluated (obtained as paraffin-embedded sections). Peripheral blood cells were analyzed by multiparameter flow cytometry and immunohistochemistry. Cytokine production was examined by enzyme-linked immunosorbent assay and intracellular cytokine staining using specific monoclonal antibodies. Synovial tissue was examined for infiltrating T cells by immunohistochemical analysis. Results We found increased numbers of circulating Th17 cells in the peripheral blood of patients with seronegative spondylarthritides (PsA and AS), but not in patients with RA or vitiligo. In addition, Th17 cells from the spondylarthritis patients showed advanced differentiation and were polyfunctional in terms of T cell receptor,driven cytokine production. Conclusion These observations suggest a role of Th17 cells in the pathogenesis of certain human autoimmune disorders, in particular the seronegative spondylarthritides. [source] Induction of triggering receptor expressed on myeloid cells 1 in murine resident peritoneal macrophages by monosodium urate monohydrate crystalsARTHRITIS & RHEUMATISM, Issue 2 2006Yousuke Murakami Objective Triggering receptor expressed on myeloid cells 1 (TREM-1) is a cell surface molecule that was recently identified on monocytes and neutrophils. TREM-1 has been implicated in the early inflammatory responses induced by microbes, but its pathophysiologic role in nonmicrobial inflammation remains unknown. In the present study, we investigated the role of TREM-1 in acute inflammation induced by monosodium urate monohydrate (MSU) crystals. Induction of TREM-1 expression by MSU crystal,stimulated murine resident peritoneal macrophages and infiltrating leukocytes in a murine air-pouch model of crystal-induced acute inflammation was determined. The biologic role of TREM-1 in crystal-induced cytokine production by resident peritoneal macrophages was also investigated. Methods TREM-1 expression by resident peritoneal macrophages and infiltrating leukocytes in a murine air-pouch model was determined by quantitative real-time polymerase chain reaction, Western blot analysis, and flow cytometry. Cytokine production by resident peritoneal macrophages after incubation with MSU crystals in the presence or absence of an anti,TREM-1 agonist antibody was determined by enzyme-linked immunosorbent assay. Results TREM-1 expression by resident peritoneal macrophages was significantly induced after stimulation with the crystals. Maximum expression of TREM-1 transcripts and protein occurred at 1 and 4 hours after exposure to the crystals, respectively. Costimulation of resident peritoneal macrophages with MSU crystals and an anti,TREM-1 agonist antibody synergistically increased the production of both interleukin-1, and monocyte chemotactic protein 1 compared with stimulation with the crystals alone. MSU crystals also induced TREM-1 expression in infiltrating leukocytes in a murine air-pouch model of crystal-induced acute inflammation. Conclusion These findings suggest that rapid induction of TREM-1 expression on resident peritoneal macrophages and neutrophils by MSU crystals may contribute to the development of acute gout through enhancement of inflammatory responses. [source] Modulation of cytokine production by dydrogesterone in lymphocytes from women with recurrent miscarriageBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 8 2005Raj Raghupathy Objective To examine the effects of dydrogesterone on the production of Th1 and Th2 cytokines by lymphocytes from women undergoing unexplained recurrent spontaneous miscarriage (RSM). Design Controlled prospective, clinical study conducted in a maternity hospital and a university-based immunology laboratory. Setting Faculty of Medicine, Kuwait University and Kuwait Maternity Hospital. Sample Thirty women with unexplained RSM. Methods Peripheral blood mononuclear cells (PBMC) from women with unexplained RSM were isolated from venous blood by density gradient sedimentation and stimulated with phytohaemagglutinin (PHA). Culture supernatants assayed for interferon (IFN)-,, tumour necrosis factor (TNF)-,, interleukin (IL)-4, IL-6 and IL-10 by ELISA. Levels of the progesterone-induced blocking factor (PIBF) were also measured. Main outcome measures Cytokine production in the presence and absence of progesterone and dydrogesterone. Results Dydrogesterone significantly inhibited the production of the Th1 cytokines IFN-, (P= 0.0001) and TNF-, (P= 0.005) and induced an increase in the levels of the Th2 cytokines IL-4 (P= 0.03) and IL-6 (P= 0.017) resulting in a substantial shift in the ratio of Th1/Th2 cytokines. The effect of dydrogesterone was blocked by the addition of the progesterone-receptor antagonist mifepristone, indicating that dydrogesterone was acting via the progesterone receptor. Dydrogesterone induced the production of PIBF. Conclusion Dydrogesterone inhibits the production of the Th1 cytokines IFN-, and TNF-, from lymphocytes and up-regulates the production of the Th2 cytokines IL-4 and IL-6, inducing a Th1 to Th2 cytokine shift. [source] Cellular autoreactivity against heat shock protein 60 in renal transplant patients: peripheral and graft-infiltrating responsesCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2006C. Caldas Summary Autoreactivity to heat shock protein 60 (Hsp60) has been implicated in the pathogenesis and regulation of chronic inflammation, especially in autoimmune diseases. In transplantation, there is a lack of information regarding the cytokine profile and specificity of cells that recognize self-Hsp60 as well as the kinetics of autoreactivity following transplantation. We studied the cellular reactivity of peripheral and graft-infiltrating lymphocytes against Hsp60 in renal transplant patients. Cytokine production induced by this protein in peripheral blood mononuclear cells indicated a predominance of interleukin (IL)-10 during the late post-transplantation period, mainly in response to intermediate and C-terminal peptides. Patients with chronic rejection presented reactivity to Hsp60 with a higher IL-10/interferon (IFN)-, ratio compared to long-term clinically stable patients. Graft-infiltrating T cell lines, cocultured with antigen-presenting cells, preferentially produced IL-10 after Hsp60 stimulation. These results suggest that, besides its proinflammatory activity, autoreactivity to Hsp60 in transplantation may also have a regulatory role. [source] Astaxanthin protects mesangial cells from hyperglycemia-induced oxidative signaling,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2008Emiko Manabe Abstract Astaxanthin (ASX) is a carotenoid that has potent protective effects on diabetic nephropathy in mice model of type 2 diabetes. In this study, we investigated the protective mechanism of ASX on the progression of diabetic nephropathy using an in vitro model of hyperglycemia, focusing on mesangial cells. Normal human mesangial cells (NHMCs) were cultured in the medium containing normal (5 mM) or high (25 mM) concentrations of D -glucose. Reactive oxygen species (ROS) production, the activation of nuclear transcription factors such as nuclear factor kappa B (NF,B) and activator protein-1 (AP-1), and the expression/production of transforming growth factor-beta 1 (TGF,1) and monocyte chemoattractant protein-1 (MCP-1) were evaluated in the presence or absence of ASX. High glucose (HG) exposure induced significant ROS production in mitochondria of NHMCs, which resulted in the activation of transcription factors, and subsequent expression/production of cytokines that plays an important role in the mesangial expansion, an important event in the pathogenesis of diabetic nephropathy. ASX significantly suppressed HG-induced ROS production, the activation of transcription factors, and cytokine expression/production by NHMCs. In addition, ASX accumulated in the mitochondria of NHMCs and reduced the production of ROS-modified proteins in mitochondria. ASX may prevent the progression of diabetic nephropathy mainly through ROS scavenging effect in mitochondria of mesangial cells and thus is expected to be very useful for the prevention of diabetic nephropathy. J. Cell. Biochem. 103: 1925,1937, 2007. © 2007 Wiley-Liss, Inc. [source] DNA damage and TNF, cytokine production in hairdressers with contact dermatitisCONTACT DERMATITIS, Issue 3 2005Delia Cavallo The present work was undertaken to study in hairdressers exposed to several irritants and allergens (prevalently hair-dyeing) and affected by hand contact dermatitis the possible correlation between exposure and direct-oxidative DNA damage, production of tumour necrosis factor alpha (TNF,) and allergic inflammatory disease. We evaluated in 19 hairdressers with hand contact dermatitis, 14 allergic contact dermatitis (ACD) and 5 irritant contact dermatitis (ICD) and in a selected control group TNF, serum levels by ELISA and direct-oxidative DNA damage by Fpg (formamido-pyrimidine-glycosylase)-modified Comet test on blood. Hairdressers were divided on the basis of number of hair-dyeing carried out weekly into 2 groups: low-exposure (<60 hair-dyeing/week) and high-exposure hairdressers (,60 hair-dyeing/week) that reflect also the exposure to other allergens and irritants and 2 different tasks (hairdressers and apprentice hairdressers, respectively). Serum levels of TNF, in hairdressers with ACD were significantly higher than controls with a correlation to exposure level. Significant DNA damage in ICD hairdressers with higher exposure as compared to controls was found. These findings suggest that occupational exposure can induce in hairdressers, particularly ICD, DNA damage, increase the TNFa levels particularly in ACD and induce allergic sensitization, suggesting a relationship between direct-oxidative DNA damage, TNF, production and allergic inflammatory disease. [source] Monocytes and T lymphocytes contribute to a predominance of interleukin 6 and interleukin 10 in systemic lupus erythematosus,CYTOMETRY, Issue 4 2009Susana Mellor-Pita Abstract Objective To investigate the contribution of T lymphocytes and monocytes to cytokine production in systemic lupus erythematosus (SLE). Methods Forty-five SLE patients and 19 healthy volunteers were included. Serum levels of tumor necrosis factor alpha (TNF,), interferon gamma (IFN,), interleukin (IL)-6, and IL10 were quantified by ELISA. The cytokine production capacities of peripheral blood mononuclear cells were assessed by culturing in vitro with PMA+Ionomycin or LPS. The intracellular cytokine expression was measured by flow cytometry in T lymphocytes and monocytes, respectively. The influence of the disease activity (measured as the SLE-disease activity index; SLEDAI) and the treatment the patients were receiving was evaluated. Results Serum IL10, IL6, and TNF, levels were increased in patients (P , 0.01), and a higher spontaneous (without stimuli) intracellular expression of IL10 in CD4+ and CD8+ T lymphocytes (P < 0.05) and of IL6 in monocytes (P = 0.01) were found. After stimulation, patients presented a higher percentage of CD4+ and CD8+ T lymphocytes producing IL4 and IL10 (P , 0.01), and of monocytes producing IL6 (P = 0.04) and IL10 (P = 0.008). The SLEDAI score was positively correlated with the percentage of CD4+IL10+ and CD8+IL10+ T lymphocytes (P < 0.01), and inversely correlated with CD8+TNF,+ (P= 0.02), CD4+IFN,+ (P = 0.04) and CD8+ IFN,+ (P = 0.002) T lymphocytes. Patients receiving high dose prednisone produced higher IL10, but they also were the patients with a more active disease. Conclusion Monocytes and T lymphocytes (CD4+ and CD8+) contribute to an overproduction of IL6 and IL10 in SLE; this correlates with the disease activity but is independent of the treatment the patients are receiving. © 2009 Clinical Cytometry Society [source] Monitoring of monocyte functional state after extracorporeal circulation: A flow cytometry studyCYTOMETRY, Issue 1 2004Silverio Sbrana Abstract Background Cardiovascular surgery with cardiopulmonary bypass (CPB) induces systemic inflammation and postoperative complications depending on pro- and anti-inflammatory mechanisms. Activated polymorphonuclear cells and monocytes may be responsible for morbidity associated with CPB. Knowledge of the monocyte functional state in particular may help to develop protective interventions. Methods Samples were drawn from venous peripheral blood (basal condition, at 4 and 24 h after CPB) and coronary blood (before and after cardioplegic arrest) of 14 patients undergoing cardiac surgery. The following phenotypic and functional parameters of the monocyte population were studied by flow cytometry: surface molecules expression (CD18, CD11a, CD11b, CD14, CD15, CD45, HLA-DR, and Toll-like receptor [TLR]-4), myeloperoxidase (MPO) content, and intracellular cytokine production (tumor necrosis factor [TNF]-,, interleukin [IL]-1,, IL-6, and IL-8). Results Cardiac surgery with CPB induced down-modulation of surface molecules expression on peripheral monocytes, especially at 24 h after CPB, for CD18, CD11a, and CD11b (P < 0.003) and for the CD15 adhesive cluster (P = 0.0028) and HLA-DR (P < 0.001). At 4 h after CPB, downregulation was observed for CD14 (P = 0.004), CD45 (P = 0.014), and CD15 (P = 0.0056). A loss of MPO was detected in venous peripheral (at 24 h after CPB, P = 0.01) or coronary (at reperfusion, P < 0.02) blood. The CD15 cluster complex exhibited a down-modulation in coronary blood (at reperfusion, P = 0.0003). Spontaneous intracellular production of IL-1,, IL-6, and IL-8 decreased at 24 h after CPB (P < 0.05). Conclusions The down-modulation of integrins and adhesive receptor expression and the loss of MPO suggest a strong activation and shedding reaction of circulating monocyte after CPB, further exacerbated by contact with coronary ischemic vessels. The changes of differentiation antigens may reflect the appearance of a partially immature population immediately after CPB. The reduced proinflammatory cytokine production, observed at 24 h after CPB, suggests a functional polarization of circulating monocytes. © 2003 Wiley-Liss, Inc. [source] Protective effect of curcumin, a Curcuma longa constituent, in early colonic inflammation in rats,DRUG DEVELOPMENT RESEARCH, Issue 6 2009Juan Manuel Sánchez-Calvo Abstract Curcumin, a polyphenol derived from the plant, Curcuma longa, has a variety of pharmacological effects, including chemotherapeutic, anti-inflammatory, antiangiogenic, and antioxidant activities. To gain a better understanding of the effects and mechanisms of action of curcumin on the acute injury caused by intra-colonic administration of acetic acid (AA) in rats, inflammation was assessed by histology and myeloperoxidase activity (MPO; an index of neutrophil infiltration in the mucosa); Th1 and Th2 cytokine production; histological and histochemical analysis of the lesions; nitrite production in colon mucosa; and the expression of iNOS, COX-1 and -2 using Western blotting and inmmunohistochemistry. We also studied the involvement of the p38 MAPK/JNK signalling pathway in the protective effect of curcumin in acute colonic inflammation. Curcumin (50,100,mg/kg/day) reduced the degree of colonic injury, the index of neutrophil infiltration and Th1 cytokine secretion, and increased IL-10 production, reduced colonic levels of nitrites, and reduced COX-2 and iNOS overexpression. A reduction in the activation of p38 and JNK MAPKs was also observed. Thus, we show that the widely used food additive, curcumin reduced the development of AA-induced colitis and alleviated the inflammatory response. Inhibition of MAPK signalling by curcumin could explain the changes on the cytokine Th1/Th2 profile, the reduction of COX-2 and iNOS signaling, as well as the decreased nitrite production in colonic mucosa, suggesting that curcumin may be useful in the treatment of ulcerative colitis. Drug Dev Res, 2009. © 2009 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||