Interferon β-1b effects on cytokine mRNA in peripheral mononuclear cells in multiple sclerosis

1996 ◽  
Vol 1 (5) ◽  
pp. 262-269 ◽  
Author(s):  
PV Byskosh ◽  
AT Reder
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Mrna Levels ◽  
Cytokine Mrna ◽  
Serum Triglycerides ◽  
Tnf Α ◽  
Before And After ◽  
Peripheral Mononuclear Cells ◽  
Ifn Γ ◽  
Polymerase Chain

IFN-β reduces the number and severity of exacerbations of multiple sclerosis (MS), presumably by modifying immune regulation. We used semiquantitative polymerase chain reaction (RT-PCR) to measure mRNA levels for cytokines before and after IFN β-1b therapy. mRNA was extracted from mononuclear cells of nine healthy controls and 31 patients with MS. Before therapy, IL-10 and leukemia inhibitory factor (UF) mRNA levels were elevated in stable MS compared to active MS. Twenty four hours after IFN β-1b treatment, mRNA levels for IL-1, IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, IFN-γ, TNF-α and UF had not changed. At 1 week, TNF-α mRNA increased and IL-10 and UF mRNA rose in 75% of patients. IL-2, IL-4, IL-12, IL-13 and IFN-γ did not change. At 3 months, cytokine mRNA returned to baseline levels. mRNA for the IFN-induced antiviral enzyme, 2, 5-OAS, rose by 24 h, peaked at 1 week, and remained elevated thereafter. Serum triglycerides and liver enzymes rose after therapy. Increased SGPT at 3 months correlated with TNF-α mRNA levels, suggesting that cytokines may cause some side effects of IFN β-1b. Baseline cytokine mRNA levels reflect disease activity, but the therapeutic effect of IFN β-1b does not appear to be explained by changes in cytokine mRNA levels.

scholarly journals Upregulation of Cytokines Is Detected in the Placentas of Cattle Infected with Neospora caninum and Is More Marked Early in Gestation When Fetal Death Is Observed

2008 ◽  
Vol 76 (6) ◽  
pp. 2352-2361 ◽  
Author(s):  
Anne Rosbottom ◽  
E. Helen Gibney ◽  
Catherine S. Guy ◽  
Anja Kipar ◽  
Robert F. Smith ◽  
...  
Keyword(s):  
Protein Expression ◽  
Fetal Death ◽  
Neospora Caninum ◽  
Late Gestation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Cytokine Mrna ◽  
Early Gestation ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT The protozoan parasite Neospora caninum causes fetal death after experimental infection of pregnant cattle in early gestation, but the fetus survives a similar infection in late gestation. An increase in Th1-type cytokines in the placenta in response to the presence of the parasite has been implicated as a contributory factor to fetal death due to immune-mediated pathological alterations. We measured, using real-time reverse transcription-PCR and enzyme-linked immunosorbent assay, the levels of cytokines in the placentas of cattle experimentally infected with N. caninum in early and late gestation. After infection in early gestation, fetal death occurred, and the levels of mRNA of both Th1 and Th2 cytokines, including interleukin-2 (IL-2), gamma interferon (IFN-γ), IL-12p40, tumor necrosis factor alpha (TNF-α), IL-18, IL-10, and IL-4, were significantly (P < 0.01) increased by up to 1,000-fold. There was extensive placental necrosis and a corresponding infiltration of CD4+ T cells and macrophages. IFN-γ protein expression was also highly increased, and a modest increase in transforming growth factor β was detected. A much smaller increase in the same cytokines and IFN-γ protein expression, with minimal placental necrosis and inflammatory infiltration, occurred after N. caninum infection in late gestation when the fetuses survived. Comparison of cytokine mRNA levels in separated maternal and fetal placental tissue that showed maternal tissue was the major source of all cytokine mRNA except for IL-10 and TNF-α, which were similar in both maternal and fetal tissues. These results suggest that the magnitude of the cytokine response correlates with but is not necessarily the cause of fetal death and demonstrate that a polarized Th1 response was not evident in the placentas of N. caninum-infected cattle.

scholarly journals Coinfection with Enterohepatic Helicobacter Species Can Ameliorate or Promote Helicobacter pylori-Induced Gastric Pathology in C57BL/6 Mice

2011 ◽  
Vol 79 (10) ◽  
pp. 3861-3871 ◽  
Author(s):  
Zhongming Ge ◽  
Yan Feng ◽  
Sureshkumar Muthupalani ◽  
Laura Lemke Eurell ◽  
Nancy S. Taylor ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Interleukin 17 ◽  
Mrna Levels ◽  
Cytokine Mrna ◽  
Content Type ◽  
Time Points ◽  
Gastric Pathology ◽  
Tnf Α ◽  
Ifn Γ ◽  
H Pylori

ABSTRACTTo investigate how different enterohepaticHelicobacterspecies (EHS) influenceHelicobacter pylorigastric pathology, C57BL/6 mice were infected withHelicobacter hepaticusorHelicobacter muridarum, followed byH. pyloriinfection 2 weeks later. Compared toH. pylori-infected mice, mice infected withH. muridarumandH. pylori(HmHp mice) developed significantly lower histopathologic activity index (HAI) scores (P< 0.0001) at 6 and 11 months postinoculation (MPI). However, mice infected withH. hepaticusandH. pylori(HhHp mice) developed more severe gastric pathology at 6 MPI (P= 0.01), with a HAI at 11 MPI (P= 0.8) similar to that ofH. pylori-infected mice.H. muridarum-mediated attenuation of gastritis in coinfected mice was associated with significant downregulation of proinflammatory Th1 (interlukin-1beta [Il-1β], gamma interferon [Ifn-γ], and tumor necrosis factor-alpha [Tnf-α]) cytokines at both time points and Th17 (Il-17A) cytokine mRNA levels at 6 MPI in murine stomachs compared to those ofH. pylori-infected mice (P< 0.01). Coinfection withH. hepaticusalso suppressedH. pylori-induced elevation of gastric Th1 cytokinesIfn-γandTnf-α(P< 0.0001) but increased Th17 cytokine mRNA levels (P= 0.028) at 6 MPI. Furthermore, mRNA levels ofIl-17Awere positively correlated with the severity of helicobacter-induced gastric pathology (HhHp>H. pylori>HmHp) (at 6 MPI,r2= 0.92,P< 0.0001; at 11 MPI,r2= 0.82,P< 0.002). Despite disparate effects on gastritis, colonization levels of gastricH. pyloriwere increased in HhHp mice (at 6 MPI) and HmHp mice (at both time points) compared to those in mono-H. pylori-infected mice. These data suggest that despite consistent downregulation of Th1 responses, EHS coinfection either attenuated or promoted the severity ofH. pylori-induced gastric pathology in C57BL/6 mice. This modulation was related to the variable effects of EHS on gastric interleukin 17 (IL-17) responses toH. pyloriinfection.

scholarly journals Resistance of CD7-deficient Mice to Lipopolysaccharide-induced Shock Syndromes

1999 ◽  
Vol 189 (6) ◽  
pp. 1011-1016 ◽  
Author(s):  
Gregory D. Sempowski ◽  
David M. Lee ◽  
Richard M. Scearce ◽  
Dhavalkumar D. Patel ◽  
Barton F. Haynes
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Nk Cell ◽  
Immunoglobulin Superfamily ◽  
High Dose ◽  
Mrna Levels ◽  
Lps Challenge ◽  
Tnf Α ◽  
Ifn Γ ◽  
Deficient Mice

CD7 is an immunoglobulin superfamily molecule involved in T and natural killer (NK) cell activation and cytokine production. CD7-deficient animals develop normally but have antigen-specific defects in interferon (IFN)-γ production and CD8+ CTL generation. To determine the in vivo role of CD7 in systems dependent on IFN-γ, the response of CD7-deficient mice to lipopolysaccharide (LPS)-induced shock syndromes was studied. In the high-dose LPS-induced shock model, 67% of CD7-deficient mice survived LPS injection, whereas 19% of control C57BL/6 mice survived LPS challenge (P &lt; 0.001). CD7-deficient or C57BL/6 control mice were next injected with low-dose LPS (1 μg plus 8 mg D-galactosamine [D-gal] per mouse) and monitored for survival. All CD7-deficient mice were alive 72 h after injection of LPS compared with 20% of C57BL/6 control mice (P &lt; 0.001). After injection of LPS and D-gal, CD7-deficient mice had decreased serum IFN-γ and tumor necrosis factor (TNF)-α levels compared with control C57BL/6 mice (P &lt; 0.001). Steady-state mRNA levels for IFN-γ and TNF-α in liver tissue were also significantly decreased in CD7-deficient mice compared with controls (P &lt; 0.05). In contrast, CD7-deficient animals had normal liver interleukin (IL)-12, IL-18, and interleukin 1 converting enzyme (ICE) mRNA levels, and CD7-deficient splenocytes had normal IFN-γ responses when stimulated with IL-12 and IL-18 in vitro. NK1.1+/ CD3+ T cells are known to be key effector cells in the pathogenesis of toxic shock. Phenotypic analysis of liver mononuclear cells revealed that CD7-deficient mice had fewer numbers of liver NK1.1+/CD3+ T cells (1.5 ± 0.3 × 105) versus C57BL/6 control mice (3.7 ± 0.8 × 105; P &lt; 0.05), whereas numbers of liver NK1.1+/CD3− NK cells were not different from controls. Thus, targeted disruption of CD7 leads to a selective deficiency of liver NK1.1+/ CD3+ T cells, and is associated with resistance to LPS shock. These data suggest that CD7 is a key molecule in the inflammatory response leading to LPS-induced shock.

scholarly journals Alterations in IL-6, IL-8, GM-CSF. TNF-α, and IFN-γ Release by Peripheral Mononuclear Cells in Patients with Active Vitiligo

1997 ◽  
Vol 108 (4) ◽  
pp. 527-529 ◽  
Author(s):  
Hsin-Su Yu ◽  
Kee-Lung Chang ◽  
Chia-Li Yu ◽  
Hui-Fang Li ◽  
Meng-Tse Wu ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Gm Csf ◽  
Tnf Α ◽  
Peripheral Mononuclear Cells ◽  
Ifn Γ

Immunosuppressive Activity of Sera from Patients with Colorectal and Gynecological Carcinomas as Evaluated by Impaired IFN-γ, IL-1α and TNF-α Production of Human Peripheral Mononuclear Cells

Immunobiology ◽  
1996 ◽  
Vol 196 (4) ◽  
pp. 356-362 ◽  
Author(s):  
Reinhild Muster-Bloy ◽  
Ursula Elsäser-Beile ◽  
Walter Weber ◽  
Jürgen Schulte Monting ◽  
Sabine von Kleist
Keyword(s):  
Mononuclear Cells ◽  
Immunosuppressive Activity ◽  
Tnf Α ◽  
Peripheral Mononuclear Cells ◽  
Ifn Γ

Analysis of an interferon-γ gene dinucleotide-repeat polymorphism in Nordic multiple sclerosis patients

2001 ◽  
Vol 7 (3) ◽  
pp. 157-163 ◽  
Author(s):  
Y Dai ◽  
T Masterman ◽  
W X Huang ◽  
M Sandberg-Wollheim ◽  
M Laaksonen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Dinucleotide Repeat ◽  
Mrna Levels ◽  
Peripheral Blood Mononuclear ◽  
Sibling Pairs ◽  
Genotype Frequencies ◽  
Ifn Γ ◽  
Multiple Sclerosis Patients

The proinflammatory cytokine interferon (IFN)-γ has been shown to influence the course of multiple sclerosis (MS). The IFN-γ (IFNG) contains a multiallelic dinucleotide repeat in intron l. To investigate whether alleles at this locus influence susceptibility to MS, we performed linkage and familial association analyses on 100 sibling pairs from four Nordic countries, and case-control association analysis on 220 intermediately disabled sporadic MS patients and 266 controls. To determine the effect of the polymorphism on disease outcome, we compared genotype frequencies in the most and least disabled octiles of a total cohort of 913 cases. We also measured IFN-γ mRNA levels in unstimulated peripheral blood mononuclear cells from 46 MS patients and 27 controls grouped according to IFNG intron l genotype. Both nonparametric linkage analysis and transmission disequilibrium testing of the 100 sibling pairs produced negative results. Genotype frequencies for intermediate-MS patients did not differ significantly from those for controls; nor did genotype frequencies in the benign-MS octile differ significantly from those in the severe-MS octile. Comparison of IFN-γ mRNA levels in genotype-conditioned subgroups revealed no significant differences. Thus, alleles at the IFNG intron l dinucleotide repeat appear to affect neither MS susceptibility and severity nor IFN-γ mRNA expression in vivo.

scholarly journals Vitamin D Status Modulates Inflammatory Response in HIV+ Subjects: Evidence for Involvement of Autophagy and TG2 Expression in PBMC

2020 ◽  
Vol 21 (20) ◽  
pp. 7558
Author(s):  
Monica Currò ◽  
Giuseppa Visalli ◽  
Giovanni Francesco Pellicanò ◽  
Nadia Ferlazzo ◽  
Maria Giovanna Costanzo ◽  
...  
Keyword(s):  
Vitamin D ◽  
Inflammatory Response ◽  
Vitamin D Deficiency ◽  
Mononuclear Cells ◽  
Tissue Transglutaminase ◽  
Mrna Levels ◽  
Vitamin D Status ◽  
Markers Of Inflammation ◽  
Tnf Α ◽  
Ifn Γ

Conflicting results on the involvement of vitamin D deficiency in inflammatory and immune response in HIV+ subjects are reported. We aimed to characterize the possible influence of vitamin D status on changes in expression of tissue transglutaminase gene (TGM2) and other genes involved in inflammatory response and autophagy in peripheral blood mononuclear cells (PBMC) from HIV+ subjects. HIV+ subjects (n = 57) under antiretroviral therapy (ART) and healthy controls (n = 40) were enrolled. mRNA levels of 1-alpha-hydroxylase (CYP27B1), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), TGM2, microtubule-associated protein 1A/1B-light chain 3 (LC3), autophagy-related 5 homolog (ATG5), and Beclin 1 (BECN1) were quantified by real-time PCR. In HIV+ subjects, 25(OH)D3 plasma levels were negatively correlated with time since HIV diagnosis. In PBMC from HIV+ subjects, increases in gene expression of TNF-α and IFN-γ in comparison to controls were observed. The highest increase in TNF-α transcripts was observed in HIV+ subjects with deficient 25(OH)D3 levels. Autophagy-related genes LC3, ATG5, and BECN1 were down-regulated in HIV+ subjects. Moreover, TGM2 transcripts were up-regulated in PBMC from HIV+ subjects with 25(OH)D3 deficiency. Changes observed in PBMC from HIV+ subjects appeared to be dependent on vitamin D status. The present results suggest that vitamin D deficiency is associated with changes in the expression of markers of inflammation and autophagy, resulting in immune cell dysfunction.

scholarly journals Cytokine responses to acute and chronic exercise in multiple sclerosis

2008 ◽  
Vol 104 (6) ◽  
pp. 1697-1702 ◽  
Author(s):  
Vanessa Castellano ◽  
Darpan I. Patel ◽  
Lesley J. White
Keyword(s):  
Multiple Sclerosis ◽  
Control Subjects ◽  
Cytokine Responses ◽  
Tnf Α ◽  
Single Bout ◽  
Before And After ◽  
Ifn Γ ◽  
Cycle Training ◽  
And Control ◽  
The Impact

Regular exercise reduces functional loss associated with multiple sclerosis (MS). However, the impact of exercise on inflammatory mediators associated with disease activity remains relatively unexplored. The purpose of this study was to determine whether ambulatory MS subjects would respond similarly to aerobic cycle training compared with matched controls on circulating immune variables, interleukin (IL)-6, tumor necrosis factor (TNF)-α and interferon (IFN)-γ. Eleven MS and 11 non-MS control subjects (8 women and 3 men in both groups) matched in age, height, body mass, body fat, and peak O2 uptake completed the study. Subjects completed 30 min of cycle ergometry at 60% of peak O2 uptake, 3 day/wk for 8 wk. Plasma cytokine concentrations were determined before and after exercise at weeks 0, 4, and 8. MS and control subjects showed a similar cytokine responses to exercise. IL-6 at rest tended to decrease ( P = 0.08) with training in both groups. Resting plasma TNF-α tended to be higher in MS compared with controls throughout the study ( P = 0.08). MS subjects showed elevated resting TNF-α in MS at the end of the 8-wk program ( P = 0.04), whereas resting TNF-α remained unchanged in controls ( P > 0.05). Resting plasma IFN-γ at rest was elevated in MS subjects ( P = 0.008) and unchanged in controls at the end of the intervention ( P > 0.05). The response of plasma IL-6, TNF-α, and IFN-γ after a single bout of exercise was similar between MS and control subjects ( P > 0.05). Additional research to understand the impact of exercise on immune variables in MS is warranted.

scholarly journals Proinflammatory and Immunomodulatory Cytokine mRNA Time Course Profiles in Hamsters Infected with a Virulent Variant of Leptospirainterrogans

2006 ◽  
Vol 74 (7) ◽  
pp. 4172-4179 ◽  
Author(s):  
Frédérique Vernel-Pauillac ◽  
Fabrice Merien
Keyword(s):  
Time Course ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Interleukin 2 ◽  
Leptospira Interrogans ◽  
Cytokine Mrna ◽  
Expression Levels ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT In order to quantify in vivo the mRNAs of cytokines which play important roles in leptospirosis, we have developed quantitative real-time PCR assays for interleukin-2 (IL-2), IL-4, IL-10, IL-12p40, tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), transforming growth factor β, and two housekeeping genes (encoding β-actin and hypoxanthine phosphoribosyltransferase). We used a lethal hamster model reflecting severe leptospirosis in humans. The LightCycler system was used to quantify the gene expression levels with the SYBR green I detection format using external standard curves for each target. We compared the expression levels of cytokine mRNA in the peripheral blood mononuclear cells of both control (uninfected) hamsters and Leptospira interrogans-inoculated hamsters from 1 to 24 h and then 1 to 4 days postinfection. In this kinetic study, there was pronounced expression of Th1 cytokine mRNA (TNF-α, IFN-γ, and IL-12), with transcripts being detected as early as 1 h postinfection. Expression of anti-inflammatory cytokines, such as IL-4 and IL-10, was prominent in delayed samples from 1 to 4 days postinfection in response to infection with Leptospira interrogans. Our data are the first to establish that pathogenic leptospires can stimulate in vivo the production of type 1 cytokines involved in cellular immunity by using this informative animal model. Measuring and assessing cytokine profiles may provide a useful method for accurate study of the mechanisms of anti-Leptospira immunity, indications of prognosis factors, and prospective evaluation of leptospirosis vaccine efficacy in humans.

scholarly journals Changes in intestinal Toll-like receptors and cytokines precede histological injury in a rat model of necrotizing enterocolitis

2009 ◽  
Vol 297 (3) ◽  
pp. G442-G450 ◽  
Author(s):  
Yuying Liu ◽  
Limin Zhu ◽  
Nicole Y. Fatheree ◽  
Xiaoqin Liu ◽  
Susan E. Pacheco ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Necrotizing Enterocolitis ◽  
Tissue Injury ◽  
Mrna Levels ◽  
Toll Like Receptors ◽  
Rat Pups ◽  
Tnf Α ◽  
Ifn Γ ◽  
Polymerase Chain ◽  
Neonatal Necrotizing Enterocolitis

It is unclear whether the broad inflammatory response shown in neonatal necrotizing enterocolitis (NEC) is the cause or the effect of tissue injury. Toll-like receptors (TLRs) on intestinal dendritic, mononuclear, and epithelial cells recognize bacterial ligands and damaged tissues, thus activating the inflammatory response. The present study aimed to determine whether active TLR signaling would precede histological injury in NEC. Newborn rat pups were divided into four groups: dam fed, dam fed-hypoxic, formula fed, and formula fed-hypoxic (NEC). The ileal tissues were evaluated for NEC scores at 24, 48, 72, and 120 h. Quantitative real-time reverse transcription-polymerase chain reaction and immunohistochemistry were used to measure and localize intestinal TLRs. Cytokines were assessed by a multispot cytokine array. Among the four groups, ileal injury was seen only after 72 h of formula feeding and hypoxia. We found selective induction of mRNA levels in NEC compared with dam-fed controls for TLR2 > TLR4 > TLR1 = TLR3, TLR7, and TLR9 > TLR6 ( P < 0.01); TLR5 was downregulated ( P < 0.01). All TLR changes started at 48 h, before any histological evidence of NEC. Both Th1-type cytokines (IFN-γ, IL-1β, TNF-α, and KC/GRO) and Th2-type cytokines (IL-4, IL-5 and IL-13) were significantly increased in NEC but also in nondamaged formula-fed rat ileum. In conclusion, the intestinal expression of TLRs and cytokines precedes histological injury in the experimental NEC.

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