scholarly journals Exogenous Farnesol Interferes with the Normal Progression of Cytokine Expression during Candidiasis in a Mouse Model

2007 ◽  
Vol 75 (8) ◽  
pp. 4006-4011 ◽  
Author(s):  
Dhammika H. M. L. P. Navarathna ◽  
Kenneth W. Nickerson ◽  
Gerald E. Duhamel ◽  
Thomas R. Jerrels ◽  
Thomas M. Petro
Keyword(s):  
Interleukin 2 ◽  
Sublethal Dose ◽  
Enzyme Linked Immunosorbent Assay ◽  
Th2 Cytokines ◽  
Systemic Candidiasis ◽  
Dimorphic Fungus ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ ◽  
Th1 Cytokines

ABSTRACT Candida albicans, a dimorphic fungus composed of yeast and mycelial forms, is the most common human fungal pathogen. Th1 cytokines such as interleukin-2 (IL-2), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), which are induced by macrophage IL-12, are critical to resistance against systemic candidiasis, while Th2 cytokines such as IL-4 and IL-5 are less critical. Farnesol is a quorum-sensing molecule produced by C. albicans that controls the formation of mycelia but is also a virulence factor. To determine whether farnesol enhances the virulence of C. albicans by modulating the production of Th1 and Th2 cytokines, mice were pretreated with farnesol prior to intravenous infection with a sublethal dose of farnesol-producing C. albicans. Production of IL-2, IL-4, IL-5, TNF-α, IFN-γ, and IL-12 was evaluated by bead-array flow cytometry and enzyme-linked immunosorbent assay. Mice exhibited an elevation in serum TNF-α levels at 48 h and an elevation in IFN-γ and IL-12 levels at 6 to 12 h after infection with C. albicans. Pretreatment with farnesol significantly reduced the elevation of both IFN-γ and IL-12 but not TNF-α. In contrast, mice pretreated with farnesol exhibited an unexpected elevation in IL-5 levels. To determine whether farnesol has a direct effect on macrophage production of IL-12, peritoneal macrophages were pretreated with farnesol prior to stimulation with IFN-γ plus lipopolysaccharide (LPS). Farnesol inhibited production of both IL-12 p40 and p70 from IFN-γ/LPS-stimulated macrophages. Therefore, the role of farnesol in systemic candidiasis is likely due to its ability to inhibit the critical Th1 cytokines IFN-γ and IL-12 and perhaps to enhance a Th2 cytokine, IL-5.

scholarly journals Serum Cytokine Responses in Primary Pneumonic Plague Patients

2010 ◽  
Vol 18 (1) ◽  
pp. 184-186 ◽  
Author(s):  
Xiaoyi Wang ◽  
Zuyun Wang ◽  
Zhaobiao Guo ◽  
Baiqing Wei ◽  
Fuzhang Tian ◽  
...  
Keyword(s):  
Time Course ◽  
Interleukin 2 ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Necrosis Factor Alpha ◽  
Pneumonic Plague ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACTThe serum levels of interleukin-2 (IL-2), gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-4, IL-6, and IL-10 of pneumonic plague patients were determined by enzyme-linked immunosorbent assay. IL-6 was the only elevated cytokine in the patients, and its level increased with a clear time course, indicating that IL-6 might be a prognostic marker for predicting the progression of plague.

Paracoccidioidomycosis: characterization of subpopulations of macrophages and cytokines in human mucosal lesions

2018 ◽  
Vol 57 (6) ◽  
pp. 757-763 ◽  
Author(s):  
C Pagliari ◽  
L Kanashiro-Galo ◽  
A C C Jesus ◽  
M G Saldanha ◽  
M N Sotto
Keyword(s):  
Th2 Cytokines ◽  
Arginase 1 ◽  
Immunohistochemistry Analysis ◽  
Tnf Α ◽  
Ifn Γ ◽  
Mucosal Lesions ◽  
Th1 Cytokines ◽  
Necrosis Factor ◽  
Number Of Cells

AbstractMucosal lesions of paracoccidioidomycosis (PCM) are frequently described and clinically important. Macrophages are classified as M1 or M2. M1 are proinflammatory and M2 are related to chronicity. Dectin-1 recognizes β-glucan and plays an important role against fungal cells. The objective was to verify the presence of M1, M2, and dectin-1 and a possible correlation with Th1/Th2 cytokines in mucosal PCM lesions. In sum, 33 biopsies of oral PCM were submitted to histological and immunohistochemistry analysis, and positive cells were quantified. Eleven biopsies were characterized by compact granulomas (G1), 12 with loose granulomas (G2), and 10 with both kind of granulomas (G3). pSTAT-1 was equally increased in the three groups. G1 was characterized by an increased number of CD163+ macrophages. G2 presented similar number of arginase 1, iNOS, and CD163 expressing cells. G3 presented an increased number of cells expressing arginase 1 and CD163 over iNOS. G1 and G3 presented high number of cells expressing interferon (IFN)-γ; interleukin (IL) 5 was increased in G2 and G3; the expression of IL10 was similar among the three groups, and the expression of tumor necrosis factor (TNF)-α was higher in G3. G1 correlates to Th1 cytokines and pSTAT-1 and G2 correlates to Th2 cytokines. G3 presents both kinds of cytokines. We could not associate the expression of arginase-1, CD163, iNOS, and dectin-1 with the pattern of cytokines or kind of granuloma.

scholarly journals Respiratory Tract Infection with Mycoplasma pneumoniae in Interleukin-12 Knockout Mice Results in Improved Bacterial Clearance and Reduced Pulmonary Inflammation

2006 ◽  
Vol 75 (1) ◽  
pp. 236-242 ◽  
Author(s):  
C. M. Salvatore ◽  
M. Fonseca-Aten ◽  
K. Katz-Gaynor ◽  
A. M. Gomez ◽  
A. Mejias ◽  
...  
Keyword(s):  
Respiratory Disease ◽  
Mycoplasma Pneumoniae ◽  
Pulmonary Inflammation ◽  
Airway Hyperreactivity ◽  
Interleukin 12 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Wild Type ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT Mycoplasma pneumoniae is a leading cause of pneumonia and is associated with asthma. Evidence links M. pneumoniae respiratory disease severity with interleukin-12 (IL-12) concentration in respiratory secretions. We evaluated the microbiologic, inflammatory, and pulmonary function indices of M. pneumoniae pneumonia in IL-12 (p35) knockout (KO) mice and wild-type (WT) mice to determine the role of IL-12 in M. pneumoniae respiratory disease. Eight-week-old wild-type BALB/c mice and 8-week-old IL-12 (p35) KO BALB/c mice were inoculated once intranasally with 107 CFU of M. pneumoniae. Mice were evaluated at days 2, 4, and 7 after inoculation. Outcome variables included quantitative bronchoalveolar lavage (BAL) M. pneumoniae culture, lung histopathologic scores (HPS), BAL cytokine concentrations determined by enzyme-linked immunosorbent assay (tumor necrosis factor alpha [TNF-α], gamma interferon [IFN-γ], IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor) and plethysmography, before and after methacholine, to assess airway obstruction (AO) and airway hyperreactivity (AHR). IL-12 (p35) KO mice infected with M. pneumoniae were found to have significantly lower BAL M. pneumoniae concentrations compared with M. pneumoniae-infected WT mice. Lung HPS and the parenchymal pneumonia subscores (neutrophilic alveolar infiltrate), as well as AO, were significantly lower in infected KO mice. No difference was found for AHR. Infected KO mice had significantly lower BAL concentrations of IFN-γ than WT mice; a trend toward lower BAL concentrations was observed for IL-10 (P = 0.065) and TNF-α (P = 0.078). No differences were found for IL-1β, IL-2, IL-4, IL-5, or IL-6. The lack of IL-12 in experimental M. pneumoniae pneumonia was associated with less severe pulmonary disease and more rapid microbiologic and histologic resolution.

scholarly journals Inducing Humoral and Cellular Responses to Multiple Sporozoite and Liver-Stage Malaria Antigens Using Exogenous Plasmid DNA

2013 ◽  
Vol 81 (10) ◽  
pp. 3709-3720 ◽  
Author(s):  
B. Ferraro ◽  
K. T. Talbott ◽  
A. Balakrishnan ◽  
N. Cisper ◽  
M. P. Morrow ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Elispot Assay ◽  
Intracellular Cytokine Staining ◽  
Interleukin 2 ◽  
Cellular Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Necrosis Factor Alpha ◽  
Liver Stage ◽  
Content Type ◽  
Ifn Γ

ABSTRACTA vaccine candidate that elicits humoral and cellular responses to multiple sporozoite and liver-stage antigens may be able to confer protection againstPlasmodium falciparummalaria; however, a technology for formulating and delivering such a vaccine has remained elusive. Here, we report the preclinical assessment of an optimized DNA vaccine approach that targets fourP. falciparumantigens: circumsporozoite protein (CSP), liver stage antigen 1 (LSA1), thrombospondin-related anonymous protein (TRAP), and cell-traversal protein for ookinetes and sporozoites (CelTOS). Synthetic DNA sequences were designed for each antigen with modifications to improve expression and were delivered usingin vivoelectroporation (EP). Immunogenicity was evaluated in mice and nonhuman primates (NHPs) and assessed by enzyme-linked immunosorbent assay (ELISA), gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assay, and flow cytometry. In mice, DNA with EP delivery induced antigen-specific IFN-γ production, as measured by ELISpot assay and IgG seroconversion against all antigens. Sustained production of IFN-γ, interleukin-2, and tumor necrosis factor alpha was elicited in both the CD4+and CD8+T cell compartments. Furthermore, hepatic CD8+lymphocytes produced LSA1-specific IFN-γ. The immune responses conferred to mice by this approach translated to the NHP model, which showed cellular responses by ELISpot assay and intracellular cytokine staining. Notably, antigen-specific CD8+granzyme B+T cells were observed in NHPs. Collectively, the data demonstrate that delivery of gene sequences by DNA/EP encoding malaria parasite antigens is immunogenic in animal models and can harness both the humoral and cellular arms of the immune system.

scholarly journals Effects of Toosendanin on Pregnancy and Uterine Immunity Alterations in Mice

2010 ◽  
Vol 38 (02) ◽  
pp. 319-328 ◽  
Author(s):  
Jian-Lou Zhang ◽  
Wang-Yu Shi ◽  
Wei Zhong ◽  
Ai-Tuan Ma ◽  
Xiao-Dan Wang ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Herbal Medicine ◽  
Chinese Herbal Medicine ◽  
Enzyme Linked Immunosorbent Assay ◽  
Chinese Herbal ◽  
Cd8 T Lymphocytes ◽  
Tnf Α ◽  
Ifn Γ ◽  
Th1 Cytokines ◽  
Dose Dependent

This study was conducted to explore the abortifacient effect and the mechanisms of the Chinese herbal medicine component toosendanin, and to elucidate the significance of the Th1 cytokines IFN-γ and TNF-α, CD4+ and CD8+ T lymphocytes in the occurrence of abortion. Graded doses of toosendanin were given by intraperitoneal injection (i.p.) to mice at day 5, 6, 7 of gestation. The levels of Th1 cytokines (IFN-γ, TNF-α) in serum and uterine tissues from mice sacrificed at day 8 were analyzed by enzyme linked immunosorbent assay (ELISA). Presence of T lymphocytes in endometrium was detected by immunohistochemistry. The results revealed that injection of toosendanin could produce a dose-dependent toxicity. The IFN-γ, TNF-α content in serum and uterine tissues were increased significantly. The CD4+ and CD8+ T lymphocytes were also increased in the endometrium of toosendanin treated groups. In conclusion, toosendanin is pregnancy-toxic to animals and it is relevant to the increased contents of IFN-γ, TNF-α and CD4+, CD8+ T lymphocytes.

Effects of Interferon Beta, Cyclophosphamide and Azathioprine on Cytokine Profile in Patients with Multiple Sclerosis

2005 ◽  
Vol 18 (2) ◽  
pp. 377-383 ◽  
Author(s):  
R. Totaro ◽  
A. Passacantando ◽  
T. Russo ◽  
I. Parzanese ◽  
M. Rascente ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Interferon Beta ◽  
Interleukin 2 ◽  
Interleukin 10 ◽  
Interleukin 4 ◽  
Th2 Cytokines ◽  
Positive Interaction ◽  
Tnf Α ◽  
Ifn Γ

We assessed the in vitro effects of interferon beta-1b (IFNβ-1b), cyclophosphamide (CY), and azathioprine (AZA) alone and of the combination of IFNβ-1b with CY or AZA on the production of Th1 and Th2 cytokines in 10 patients with multiple sclerosis. Cytokine levels were determined at baseline and after stimulation with IFNβ-1b, CY, and AZA alone or with the combination of IFNβ-1b with CY or AZA. The combination of IFNβ-1b with CY resulted in a statistically significant decrease in the production of interleukin-2 (IL-2) (P=0.003) and tumor necrosis factor alfa (TNF-α) (P=0.03). An additive effect on the production of interferon gamma (IFN-γ) (P=0.2) and interleukin-10 (IL-10) (P=0.6), and a positive interaction on the production of interleukin-4 (IL-4) (P=0.08) were observed although the findings were not statistically significant. The combination of IFNβ-1b with AZA resulted in a significant negative effect on the production of IL-2 (P=0.006), whereas TNF-α (P=0.02), IFN-γ (P=0.03), IL-4 (P=0.2), and IL-10 (P=0.3) were not statistically impacted. Our data show that CY was able to improve the effects of IFNβ-1b on the ratio of Th1/Th2 cytokines.

scholarly journals Th1 Cytokines Are Essential for Placental Immunity to Listeria monocytogenes

2005 ◽  
Vol 73 (10) ◽  
pp. 6322-6331 ◽  
Author(s):  
Ellen M. Barber ◽  
Melissa Fazzari ◽  
Jeffrey W. Pollard
Keyword(s):  
T Cells ◽  
Listeria Monocytogenes ◽  
Cytotoxic T Cells ◽  
Fetal Loss ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Th1 Cytokine ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Th1 Cytokines

ABSTRACT The fetal allograft poses an immunological challenge: how is it protected while immunity to pathogens, particularly those that replicate in the placenta, is maintained? Several theories have been proposed to explain this fetal protection, including a pregnancy-based bias towards a Th2 rather than Th1 cytokine profile in order to avoid generating cytotoxic T cells that could threaten the fetus. Listeria monocytogenes preferentially replicates in the placenta and systemically requires a Th1 response for sterile eradication. In the placenta, the Th1 cytokines tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) are also synthesized in response to this pathogen, without fetal loss. Here we show, by using mice homozygous for null mutations in either the cytokine or cytokine receptor genes, a requirement for both TNF-α and IFN-γ signaling for an effective placental immune response to L. monocytogenes. However, T cells were not recruited to the placenta. Genetic studies in which the fetal component of the placenta was genetically different from the mother indicated that both the production of and response to these cytokines were maternal. Despite the requirement for these cytokines, the early recruitment of neutrophils to the placenta was normal. Consequently, the bacterium appeared to be delayed in its colonization of this organ and did not fully gain hold until 72 h postinfection. These data show a requirement for Th1 cytokines during pregnancy for effective immunity and indicate that a bias away from Th1 cytokine synthesis is not a necessary prerequisite of pregnancy.

scholarly journals Comparison of Serum and Cell-Specific Cytokines in Humans

2001 ◽  
Vol 8 (6) ◽  
pp. 1097-1103 ◽  
Author(s):  
Janine Jason ◽  
Lennox K. Archibald ◽  
Okey C. Nwanyanwu ◽  
Martha G. Byrd ◽  
Peter N. Kazembe ◽  
...  
Keyword(s):  
T Cells ◽  
Interleukin 2 ◽  
Peripheral Blood Cell ◽  
Necrosis Factor Alpha ◽  
Entire Study ◽  
Serum Cytokines ◽  
Tnf Α ◽  
Immunodeficiency Virus ◽  
Factor Alpha ◽  
Ifn Γ

ABSTRACT Cytokines function at the cellular, microenvironmental level, but human cytokine assessment is most commonly done at the macro level, by measuring serum cytokines. The relationships between serum and cellular cytokines, if there are any, are undefined. In a study of hospitalized patients in Malawi, we compared cytometrically assessed, cell-specific cytokine data to serum interleukin 2 (IL-2), IL-4, IL-6, IL-8, IL-10, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) levels in 16 children and 71 (IL-2, -4, -6, -10) or 159 (IL-8, IFN-γ, and TNF-α) adults, using Wilcoxon rank sum tests and Pearson's (rp ) and Spearman's (rs ) rank correlations. For the entire study group, correlations between identical serum and cellular cytokines mainly involved IL-8 and IFN-γ, were few, and were weakly positive (r < 0.40). Blood culture-positive persons had the most and strongest correlations, including those between serum IL-2 levels and the percentages of lymphocytes spontaneously making IL-2 (rs = +0.74), serum IL-8 levels and the percentages of lymphocytes spontaneously making IL-8 (rp = +0.66), and serum IL-10 levels and the percentages of CD8+ T cells making TNF-α (rp = +0.89). Human immunodeficiency virus (HIV)-positive persons had the next largest number of correlations, including several serum IL-8 level correlations, correlation of serum IL-10 levels with the percentages of lymphocytes producing induced IL-10 (rs = +0.36), and correlation of serum IFN-γ levels and the percentages of lymphocytes spontaneously making both IL-6 and IFN-γ in the same cell (rp = +0.59). HIV-negative, malaria smear-positive, and pediatric patients had few significant correlations; for the second and third of these subgroups, serum IL-8 level was correlated with the percentage of CD8− T cells producing induced IL-8 (rs = +0.40 and rs = +0.56, respectively). Thus, the strength of associations between serum and cellular cytokines varied with the presence or absence of bloodstream infection, HIV status, and perhaps other factors we did not assess. These results strongly suggest that serum cytokines at best only weakly reflect peripheral blood cell cytokine production and balances.

scholarly journals Impact of Cethromycin (ABT-773) Therapy on Microbiological, Histologic, Immunologic, and Respiratory Indices in a Murine Model of Mycoplasma pneumoniae Lower Respiratory Infection

2004 ◽  
Vol 48 (8) ◽  
pp. 2897-2904 ◽  
Author(s):  
Ana María Ríos ◽  
Asunción Mejías ◽  
Susana Chávez-Bueno ◽  
Mónica Fonseca-Aten ◽  
Kathy Katz ◽  
...  
Keyword(s):  
Mouse Model ◽  
Mycoplasma Pneumoniae ◽  
Pulmonary Function Tests ◽  
Statistical Significance ◽  
Etiologic Agent ◽  
Whole Body ◽  
Enzyme Linked Immunosorbent Assay ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT Mycoplasma pneumoniae is a major etiologic agent of acute lower respiratory infections. We evaluated the antimicrobial and immunologic effects of cethromycin (ABT-773), a ketolide antibiotic, for the treatment of M. pneumoniae pneumonia in a mouse model. Eight-week-old BALB/c mice were inoculated intranasally once with 106 CFU of M. pneumoniae on day 0. Treatment was started 24 h after inoculation. Groups of mice were treated subcutaneously with cethromycin at 25 mg/kg of body weight or with placebo daily until sacrifice. Five to ten mice per group were evaluated at days 1, 4, 7, and 10 after inoculation. Outcome variables included bronchoalveolar lavage (BAL) for M. pneumoniae quantitative culture and cytokine and chemokine concentration determinations by enzyme-linked immunosorbent assay (tumor necrosis factor alpha [TNF-α], gamma interferon [IFN-γ], interleukin-1β [IL-1β], IL-2, IL-4, IL-12, granulocyte-macrophage colony-stimulating factor, IL-8, monocyte chemoattractant protein 1 [MCP-1], and macrophage inflammatory protein 1α [MIP-1α]), histopathologic score of the lungs (HPS), and pulmonary function tests (PFT) using whole-body, unrestrained plethysmography at the baseline and post-methacholine exposure as indicators of airway obstruction (AO) and airway hyperresponsiveness (AHR), respectively. The cethromycin-treated mice had a greater reduction in M. pneumoniae culture titers than placebo-treated mice, reaching statistical significance on days 7 and 10 (P < 0.05). HPS was significantly reduced in cethromycin-treated mice compared with placebo-treated mice on days 4, 7, and 10 (P < 0.05). Cytokine concentrations in BAL samples were reduced in mice that received cethromycin, and the differences were statistically significant for 7 of the 10 cytokines measured (TNF-α, IFN-γ, IL-1β, IL-8, IL-12, MCP-1, and MIP-1α) on day 4 (P < 0.05). PFT values were improved in the cethromycin-treated mice, with AO and AHR significantly reduced on day 4 (P < 0.05). In this mouse model, treatment with cethromycin significantly reduced M. pneumoniae culture titers in BAL samples, cytokine and chemokine concentrations in BAL samples, histologic inflammation in the lungs, and disease severity as defined by AO and AHR.

scholarly journals Variables That Affect Assays for Plasma Cytokines and Soluble Activation Markers

1999 ◽  
Vol 6 (1) ◽  
pp. 89-95 ◽  
Author(s):  
Najib Aziz ◽  
Parunag Nishanian ◽  
Ronald Mitsuyasu ◽  
Roger Detels ◽  
John L. Fahey
Keyword(s):  
Tumor Necrosis Factor ◽  
Immune Activation ◽  
Tumor Necrosis ◽  
Interleukin 2 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Prognostic Information ◽  
Necrosis Factor Alpha ◽  
Activation Markers ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT Cytokines and soluble immune activation markers that reflect cytokine activities in vivo are increasingly being measured in plasma, serum, and other body fluids. They provide useful diagnostic and prognostic information as well as insight into disease pathogenesis. Assays of neopterin, β2-microglobulin, soluble interleukin-2 receptor, and soluble tumor necrosis factor receptor type II as well as of the cytokines tumor necrosis factor alpha and gamma interferon (IFN-γ) were evaluated by using serum and plasma samples of human immunodeficiency virus (HIV)-positive and HIV-negative subjects. Many factors were found to influence the outcomes of these assays. Substantial differences in apparent levels of analytes were frequently found when enzyme-linked immunosorbent assay (ELISA) kits from different manufacturers were used. In some cases, differences were found in the standards provided by separate manufacturers. Furthermore, the analytic results from different lots of ELISA kits supplied by single manufacturers differed by as much as 50%. The need for uniformity in the standards for quantitative assays was clearly illustrated. International reference standards are available for cytokines but not for soluble cytokine receptors or soluble activation markers. Marker levels in serum or in plasma were similar except those for IFN-γ. Most of the analytes were stable under several storage conditions. Thus, batch testing of frozen stored samples is feasible. The findings indicate that for longitudinal studies, the levels of cytokines and immune activation markers in plasma or serum should be measured by using preverified reagents from one manufacturer. The quality of laboratory performance can have an impact on clinical relevance. Proficiency testing and external quality assurance programs can help to develop the needed consensus.

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