scholarly journals A rat model of exercise-induced asthma: a nonspecific response to a specific immunogen

2011 ◽  
Vol 300 (4) ◽  
pp. R917-R924 ◽  
Author(s):  
Einat Kodesh ◽  
Frank Zaldivar ◽  
Christina Schwindt ◽  
Phuc Tran ◽  
Alvin Yu ◽  
...  
Keyword(s):  
Brown Norway ◽  
Respiratory Sounds ◽  
Keratinocyte Chemoattractant ◽  
Breath Sounds ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Ifn Γ ◽  
Exercise Induced ◽  
Key Aspects ◽  
Norway Rats

Exercise-induced bronchoconstriction (EIB) is common; however, key aspects of its pathogenesis are still unclear. We investigated the feasibility of adapting an established animal model of asthma to investigate the earliest stages of EIB. The hypothesis was that a single exposure to a normally innocuous, and brief, exercise challenge could trigger EIB symptoms in rats previously sensitized to ovalbumin (OVA) but otherwise unchallenged. Brown-Norway rats were sensitized by intraperitoneal injection of OVA at 0 and 2 wk. At week 3, animals were exposed to either aerosolized OVA (SS) or exercise (EXS). A trained, blinded, clinical observer graded EIB by respiratory sounds. Plasma and lung cytokine levels were analyzed. No control rats with or without exercise (EX, CON) showed evidence of EIB. Eighty percent of the SS group demonstrated abnormal breath sounds upon exposure to aerosolized OVA. Approximately 30% of EXS rats sensitized to OVA but exposed only to exercise had abnormal breath sounds. Lung tissue levels of TNF-α, IL-1α, growth-related oncogene/keratinocyte/chemoattractant, and IFN-γ were significantly higher ( P < 0.001) in the SS group, relative to all other groups. Changes in most of these cytokines were not notable in the EXS rats, suggesting a different mechanism of EIB. Remarkably, IFN-γ, but not the other cytokines measured, was significantly elevated following brief exercise in both sensitized and unsensitized rats. Exercise led to detectable breathing sound abnormalities in sensitized rats, but less severe than those observed following classical OVA challenge. Precisely how this immune crossover occurs is not known, but this model may be useful in elucidating essential mechanisms of EIB.

The Effect of Antiretroviral Therapy on IL-6, IL-1β, TNF-α, IFN-γ Levels and their Relationship with HIV-RNA and CD4+ T Cells in HIV Patients

2020 ◽  
Vol 18 (5) ◽  
pp. 354-361
Author(s):  
Gülay Okay ◽  
Meliha Meric Koc ◽  
Eray Metin Guler ◽  
Ayşegül Yabaci ◽  
Abdürrahim Kocyigit ◽  
...  
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
Cell Count ◽  
Cd4 T Cell ◽  
Positive Correlation ◽  
Hiv Rna ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Ifn Γ ◽  
Cd4 T Cell Count

Background: Serum cytokine levels over the course of HIV infection usually increase with immunosuppression and decrease after antiretroviral treatment (ART). Objectives: The aim of the study is to compare cytokine levels between HIV-infected patients (HIP) and controls and investigate the relationship between CD4+T cell count, HIV-RNA levels, and cytokine levels. Methods: The study subjects comprised ART-naive HIP (n=30) with no comorbidities and age-and sex-matched healthy controls. We measured levels of IL-6, IL-1β, TNF-α, and IFN-γ in serum samples of HIP at the beginning and at month 6 of ART and in controls. Results: The mean age of the study subjects was 38.7 ±10.3 years, with men making up 86.7% of the study subjects (n=26). IL-6, IL-1β, and TNF-α levels were significantly higher in both ART-naive (p<0.001, p=0.002, p=0.001) and ART-experienced HIP (p<0.001) than controls. The IFN-γ level was lower in both ART-naive and ART-experienced HIP compared to controls (p=0.082 and p=0.002). There was a positive correlation between the CD4+T cell count and serum concentration of IFN- γ(r=0.320, p<0.05). While the serum IFN-γ concentration showed a negative correlation with the HIVRNA level(r=-0.412, p<0.001), the serum IL-1β, IL-6, and TNF-α concentrations showed a positive correlation with the HIV-RNA level (r=0.349, p<0.001; r:0.54, p<0.001; r:0.438, p<0.00). Conclusions: Although serum concentrations of IL-6, IL-1β and TNF-α showed a significant decrease after ART, they were still significantly higher than the controls. IFN-γ responded differently to ART compared to the other cytokines, indicating that it may play a distinct and important role in the pathogenesis of HIV infection.

scholarly journals Correlations of Expression Levels of a Panel of Genes (IRF5, STAT4, TNFSF4, MECP2, and TLR7) and Cytokine Levels (IL-2, IL-6, IL-10, IL-12, IFN-γ, and TNF-α) with Systemic Lupus Erythematosus Outcomes in Jordanian Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Amal H. Uzrail ◽  
Areej M. Assaf ◽  
Shtaywy S. Abdalla
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Renal Damage ◽  
Organ Damage ◽  
Systemic Lupus ◽  
Expression Levels ◽  
Cardiovascular Damage ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Ifn Γ

Systemic lupus erythematosus (SLE) is characterized by systemic end-organ damage. We investigated the involvement of IRF5, TLR-7, MECP2, STAT4, and TNFSF4 genes and TNF-α, IFN-γ, IL-2, IL-12, IL-6, and IL-10 cytokines in SLE pathogenesis and in organ damage in Jordanian patients. Blood was collected from 51 patients and 50 controls. Expression levels of SLE genes in PBMCs and cytokine levels were determined using RT-PCR and ELISA, respectively. Expression levels of all genes and levels of TNF-α, IL-12, IL-6, and IL-10 were higher in SLE patients than those in controls (p<0.05), whereas IL-2 level was lower. High STAT4 (α), TNFSF4, and IL-10 levels correlated with cardiovascular damage, and high MECP2 (α) and TNF-α correlated with renal damage. Pulmonary and musculoskeletal damages correlated with high levels of TNFSF4. We concluded that STAT4 and TNFSF4 genes with TNF-α and IL-10 cytokines could be used as biomarkers to assess SLE activity and manage treatment.

scholarly journals TNF-α- Mediated-p38-Dependent Signaling Pathway Contributes to Myocyte Apoptosis in Rats Subjected to Surgical Trauma

2015 ◽  
Vol 35 (4) ◽  
pp. 1454-1466 ◽  
Author(s):  
Huaxing Wu ◽  
Guonian Wang ◽  
Shuai Li ◽  
Mingyue Zhang ◽  
Hulun Li ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Flow Cytometry ◽  
Signaling Pathway ◽  
Early Stage ◽  
Surgical Trauma ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Ifn Γ ◽  
Myocyte Apoptosis ◽  
Dependent Signaling Pathway

Background: The accumulation of cytokines in the plasma after trauma can induce myocyte apoptosis. We aimed to identify which cytokine(s) present in the plasma responsible for myocyte apoptosis, and delineated the signal transduction mechanism in rats subjected to surgical trauma. Methods: Rats were randomized into two groups: control and trauma groups, which was divided into five subgroups: posttraumatic 0, 3, 6, 12, and 24 h subgroups. Cardiomyocytes isolated from traumatized rats were incubated with one of the factors for 12 h (normal plasma; Cytomix; TNF-α; IL-1β; IFN-γ; trauma plasma; anti-TNF-α antibody; SB203580). Myocyte apoptosis, cytokine levels, and MAPKs activation, as the primary experimental outcomes, were measured by TUNEL, flow cytometry, ELISA and Western blot, respectively. Results: Myocyte apoptosis was induced by surgical trauma during the early stage after trauma. Accompanying this change, plasma TNF-α, IL-1β, and IFN-γ levels were elevated in traumatized rats. Incubation of traumatized cardiomyocytes with cytomix or TNF-α alone induced myocyte apoptosis, and increased the activation of p38 and ERK1/2. Myocyte apoptosis and p38 activation were elevated in traumatized cardiomyocytes with trauma plasma, and these increases were partly abolished by anti-TNF-α antibody or SB203580. Conclusion: Our study demonstrated that there exists the TNF-α-mediated-p38-dependent signaling pathway that contributed to posttraumatic myocyte apoptosis of rats undergoing surgical trauma.

Nitric Oxide Suppresses IFN-γ Production in the Spleen of Mercuric Chloride-Exposed Brown Norway Rats

1995 ◽  
Vol 161 (2) ◽  
pp. 195-206 ◽  
Author(s):  
Peter H. van der Meide ◽  
Miranda C.D.C. de Labie ◽  
Caroline A.D. Botman ◽  
Jan Aten ◽  
Jan J. Weening
Keyword(s):  
Nitric Oxide ◽  
Mercuric Chloride ◽  
Brown Norway ◽  
Ifn Γ ◽  
Norway Rats

Abstract P182: Advanced Atherosclerosis is Associated with Systemic and End-organ Inflammation, Vascular Oxidative Stress and Endothelial Dysfunction but not Hypertension in Mice

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Quynh N Dinh ◽  
Grant R Drummond ◽  
Henry Diep ◽  
Christopher T Chan ◽  
Dorota Ferens ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
High Fat ◽  
Chronic Inflammatory Condition ◽  
Tnf Α ◽  
Brain Expression ◽  
Cytokine Levels ◽  
Ifn Γ ◽  
Vascular Oxidative Stress

Introduction: Evidence suggests that hypertension involves underlying inflammation, however whether atherosclerosis - a chronic inflammatory condition - can cause hypertension is unknown. We tested whether blood pressure (BP) is higher in high-fat fed ApoE-/- vs chow-fed wild-type (WT) mice, and whether advanced atherosclerosis is associated with systemic and end-organ inflammation, oxidative stress and endothelial dysfunction. Methods: Male ApoE-/- and WT mice were placed on high fat and chow diets, respectively, from 5-56 weeks. To clarify the effects of ageing alone, aged WT mice were compared to young chow-fed WT mice (8-12 week old). We measured systolic BP, plasma cytokine levels, mRNA expression of inflammatory markers, vascular superoxide and endothelial function. Results: There was no difference in BP of aged ApoE-/- (104.2 ± 2.9 mmHg) and age-matched WT mice (113.2 ± 1.3 mmHg) (n=13-18, P>0.05). However, plasma IL-6, TNF-α and IFN-γ were elevated in ApoE-/- by more than 2-fold vs age-matched WT (n=9-10, all P<0.05), as was brain expression of IL-1β, IL-6, TNF-α, IFN-γ, TGFβ1, CCR2, CCL2, CCL7, CCL8, CCL12 and IL-10 (n=9-10, all P<0.05), and aortic expression of IL-6, CCR2, CCL8 and CCL12 (n=6-8, all P<0.05). Ageing, but not atherosclerosis, increased renal expression of IL-1β, IL-6, TNF-α, CCR2, CCL2, CCL7, CCL8, CCL12 and Foxp3, and aortic expression of CCL2, IL-10 and Foxp3 by at least 2-fold (n=6-10, all P<0.05). In ApoE-/- aorta, Nox2-dependent superoxide production was 4-fold greater than in WT (n=5-6, P<0.05), and endothelium-dependent vasorelaxation to carbachol was markedly reduced by more than half (n=5-7, P<0.05). Ageing alone had no effect on BP, systemic inflammation or endothelial function. Conclusions: Despite the systemic and end-organ inflammation, oxidative stress and endothelial dysfunction, advanced atherosclerosis does not result in elevated BP.

scholarly journals Plasma cytokine profiles associated with rhodesiense sleeping sickness and falciparum malaria co-infection in North Eastern Uganda

2019 ◽  
Vol 15 (1) ◽  
Author(s):  
Julius Nsubuga ◽  
Charles Drago Kato ◽  
Ann Nanteza ◽  
Enock Matovu ◽  
Vincent Pius Alibu
Keyword(s):  
Transforming Growth Factor ◽  
Cytokine Response ◽  
Healthy Controls ◽  
Plasma Cytokine ◽  
Tnf Α ◽  
Significant Difference ◽  
Cytokine Levels ◽  
North Eastern ◽  
Ifn Γ ◽  
Eastern Uganda

Abstract Background Immunological Human African Trypanosomiasis (HAT) studies often exclude malaria, although both infections overlap in specific endemic areas. During this co-infection, it is not known whether this parasitic interaction induces synergistic or antagonistic cytokine response among humans. This study determined prevalence of Plasmodium falciparum malaria among Trypanosoma brucei rhodesiense HAT and plasma cytokine profile levels associated with HAT and/or malaria infections. Methods Participants were recruited at Lwala hospital in north eastern Uganda: healthy controls (30), malaria (28), HAT (17), HAT and malaria (15) diagnosed by microscopy and PCR was carried out for parasite species identification. Plasma cytokine levels of Interferon-gamma (IFN-γ), Tumour Necrosis Factor-alpha (TNF-α), Interleukin (IL)-6, IL-10 and Transforming Growth Factor-beta (TGF-β) were measured by sandwich Enzyme-Linked Immuno Sorbent Assay and data statistically analysed using Graphpad Prism 6.0. Results The prevalence of P. falciparum malaria among T. rhodesiense HAT cases was high (46.8%). Malaria and/or HAT cases presented significant higher plasma cytokine levels of IFN-γ, TNF-α, IL-6, IL-10 and TGF-β than healthy controls (P < 0.05). Levels of IFN-γ, IL-6 and IL-10 were significantly elevated in HAT over malaria (P < 0.05) but no significant difference in TNF-α and TGF-β between HAT and malaria (P > 0.05). Co-infection expressed significantly higher plasma IFN-γ, IL-6, and IL-10 levels than malaria (P < 0.05) but no significant difference with HAT mono-infection (P > 0.05). The TNF-α level was significantly elevated in co-infection over HAT or malaria mono-infections (P < 0.05) unlike TGF-β level. Significant positive correlations were identified between IFN-γ verses TNF-α and IL-6 verses IL-10 in co-infection (Spearman’s P < 0.05). Conclusions The T. b. rhodesiense significantly induced the cytokine response more than P. falciparum infections. Co-infection led to synergistic stimulation of pro-inflammatory (IFN-γ, TNF-α), and anti-inflammatory (IL-6, and IL-10) cytokine responses relative to malaria mono-infection. Level of TNF-α partially indicates the effect induced by T. b. rhodesiense and P. falciparum mono-infections or a synergistic interaction of co-infections which may have adverse effects on pathogenesis, prognosis and resolution of the infections. Trial registration VCD-IRC/021, 26/08/2011; HS 1089, 16/01/2012

Oligoclonal bands and increased cytokine levels in idiopathic intracranial hypertension

Cephalalgia ◽  
2015 ◽  
Vol 35 (13) ◽  
pp. 1153-1161 ◽  
Author(s):  
Güneş Altıokka-Uzun ◽  
Erdem Tüzün ◽  
Esme Ekizoğlu ◽  
Canan Ulusoy ◽  
Sibel Yentür ◽  
...  
Keyword(s):  
Intracranial Hypertension ◽  
Idiopathic Intracranial Hypertension ◽  
Vision Loss ◽  
Oligoclonal Bands ◽  
Control Groups ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Immunologic Factors ◽  
Ifn Γ ◽  
And Control

Objectives The pathogenesis of idiopathic intracranial hypertension (IIH) is currently unknown and there are speculations about the contribution of some immunologic factors. The aim of this study is to investigate the presence of oligoclonal bands (OCBs) and cerebrospinal fluid (CSF) and/or serum cytokine levels in patients with IIH. Methods Patients fulfilling revised diagnostic criteria for IIH were included. Their demographic, clinical, ophthalmologic and laboratory features were examined. Serum and CSF samples were detected by isoelectric focusing and immunoblotting for OCBs. The samples of IIH patients and control groups were investigated by ELISA for cytokine levels. Results We detected OCBs in eight (30.77%) patients diagnosed with IIH. There were no other obvious clinical and laboratory differences of IIH profiles between the patients with and without OCBs, but frequency of vision loss was significantly higher in the group with OCBs in comparison to OCB negatives ( p = 0.038). Patients with IIH had highly elevated TNF-α, IFN-γ, IL-4, IL-10, IL-12, IL-17 in their sera compared to patients with multiple sclerosis (MS) and healthy controls. Furthermore, all cytokines except TNF-α in the CSF were found significantly higher in IIH patients compared to MS controls. Conclusion The presence of OCBs and elevated cytokine levels in IIH patients may support an immunologic background in the pathophysiological pathway of this disorder.

Correlative Analysis and Clinical Update Of a Phase II Study Using Lenalidomide and Rituximab In Patients With Indolent Non-Hodgkin Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 249-249
Author(s):  
Samuel Yamshon ◽  
Lihong Qi ◽  
Chaoyu Yu ◽  
Xiao-Dong Li ◽  
Robert O'Donnell ◽  
...  
Keyword(s):  
Phase Ii ◽  
Clinical Activity ◽  
Serum Cytokine ◽  
Gm Csf ◽  
Tnf Α ◽  
Significant Difference ◽  
Cytokine Levels ◽  
Ifn Γ ◽  
Time Point

Abstract Background Although indolent non-Hodgkin lymphomas (iNHLs) are responsive to initial therapy, patients have a relapsing and progressive disease course and most remain incurable with current treatments. Lenalidomide is an immunomodulatory agent that enhances rituximab-mediated antibody-dependent cellular cytotoxicity. In lymphoma cell lines, animal models, and in several phase II trials, combining lenalidomide and rituximab (R2) resulted in improved antitumor activity relative to either agent alone. However, the immunological mechanisms remain unclear. Here we provide updated results from a phase II trial investigating the clinical activity of R2 in previously untreated and relapsed/refractory (R/R) patients with iNHL. We also present an analysis of immunologic correlative data that may provide insight into the therapy's mechanism-of-action and may also predict response. Aims Study aims were to assess: the clinical activity of the R2 regimen in previously untreated and R/R iNHL patients and, assess the potential of serum cytokine levels to predict response. Methods Patients had previously untreated (n=15) or R/R (n=30) iNHL with measurable disease, and ECOG Performance Status ² 2. Lenalidomide (20 mg/day) was administered on days 1–21 of a 28-day cycle and continued until disease progression, rituximab 375 mg/m2 IV was administered on day 15 of cycle 1 and repeated weekly for a total of 4 doses. The primary clinical endpoint was overall response rate (ORR). Secondary endpoints included response duration (DR), overall survival, progression-free survival (PFS), and safety. The correlative serum cytokine samples were obtained from patients at baseline, D15 (prior to treatment with rituximab), D30 and D60. IL-1, 2, 6, 8, 10, 12, GM-CSF, IFN-γ, TNF-α , CXCL-10/IP-10 levels were measured at each time point using a Meso Scale Discovery multi-plex cytokine assay. The cytokine levels at each time point were then correlated with response using a two-sided T test. Results Of the 30 R/R patients, 22 had follicular lymphoma (FL), the median age was 60 years, median number of prior therapies was 3 (range 1–11), and 50% were refractory to rituximab. Of the 15 previously untreated patients, 12 had FL and the median age was 58. For the 27 evaluable R/R patients, the ORR was 74%, including 12 patients (44%) with a CR. At a median follow-up of 34 months, median PFS was 12.4 months, the median DR and time to next therapy (TTNT) were 15.4 and 37.4 months respectively with 7 remissions that are ongoing including three that have lasted more than 48 months. Of the 15 previously untreated patients 13 are evaluable for response; the ORR was 92% with 6 of 13 (42%) having a CR. At a median follow-up of 18 months the median PFS is 14.5 months; the median DR has not been reached. The correlative analyses showed that there was a significant increase in IFN-γ, GM-CSF, CXCL-10 and IL-2 at Day 15 with a 652, 494, 737, and 242% increase respectively above baseline which correlated with patients who had a CR (p < 0.05), Table. IL-1, 6, 8, 10, 12, and TNF-α were also measured, but did not predict CR at any time point. Phenotypic and functional analyses are ongoing. There was no significant difference in the percent increase in cytokine levels in previously untreated versus R/R patients. Conclusion The R2 regimen has considerable activity in patients with both untreated or R/R iNHL, particularly those with FL. A significant increase in the serum levels of IFN-γ, GM-CSF, IL-2 and CXCL-10/IP-10 after 2 weeks of lenalidomide alone correlates with achievement of CR. Disclosures: Off Label Use: The use of lenalidomide for the treatment of indolent NHL will be discussed which is not an FDA approved indication. Tuscano:Celgene: Honoraria, Research Funding.

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