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

scholarly journals Alteration of Serum Levels of Cytokines in Schizophrenic Patients before and after Treatment with Risperidone

2019 ◽  
Author(s):  
Esfandiar Azizi ◽  
Ahmad Zavaran Hosseini ◽  
Sara Soudi ◽  
Ahmad Ali Noorbala
Keyword(s):  
Healthy Subjects ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Syndrome Scale ◽  
Tnf Α ◽  
Significant Difference ◽  
Before And After ◽  
Schizophrenic Patients ◽  
Ifn Γ

A growing body of evidence suggests the existence of abnormalities in the immune system of schizophrenic patients. The current study examined serum levels of interleukin (IL) -1β, IL-6, IL-2,interferon(IFN) -γ, and tumor necrosis factor(TNF)-α in schizophrenic patients before and after treatment with risperidone and correlated levels of these cytokines with symptomatology. The study group consisted of 24 schizophrenic patients as defined by Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria and 24 healthy controls. Serum cytokine levels were examined using enzyme-linked immunosorbent assay (ELISA). Schizophrenic symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS) questionnaire. The serum levels of TNF-α, IL-1β and IL-6 were significantly higher in participants before treatment compared with the healthy controls and after treatment (p<0.001). IFN-γ and IL-2 levels were significantly lower in participants after treatment compared with before treatment and the healthy controls (p<0.001). Except for IL-6 (p<0.05), there was no significant difference in the levels of TNF-α and IL-1β between the patients receiving treatment and the healthy subjects. Moreover, there was no significant difference in levels of IFN-γ and IL-2 between patients before treatment and the healthy subjects. There were no significant correlations between the concentration of cytokines studied and the PANSS. Positive intercorrelations between the production of IFN-γ and IL-2 were detected for sums of all groups(r=0.33, p=0.005). Clinical improvement of treated patients was associated with a reduction in the studied cytokines. It seems that changes in the cytokines level may play a significant role in the psychopathology of these patients.

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.

scholarly journals Elevated frequencies of total and MAIT cell subsets in patients with knee osteoarthritis

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7443
Author(s):  
Ding Zhao ◽  
Wei Zhong ◽  
Dongfeng Han ◽  
Yingbo Li ◽  
Yanfang Jiang ◽  
...  
Keyword(s):  
Binary Logistic Regression ◽  
Binary Logistic Regression Analysis ◽  
Clinical Parameters ◽  
Healthy Controls ◽  
Plasma Cytokine ◽  
Mait Cells ◽  
Knee Oa ◽  
Cytokine Levels ◽  
Ifn Γ ◽  
And Gender

Background Osteoarthritis (OA) is characterized by the degeneration of joint cartilage, with concomitant changes in the synovium and subchondral bone. Recently, the inflammatory response and involvement of several types of T-cells has been implicated in the development of OA. This study investigated the frequency of MR1-restricted mucosal-associated invariant T (MAIT) cells in patients with knee OA. Methods Forty-five patients recently diagnosed with knee OA and 21 age- and gender-matched healthy controls were recruited for this study. Percentages of circulating MAIT cells were assessed by flow cytometry. Plasma cytokine levels were measured using cytometric bead arrays. Associations between the percentages of MAIT cells, plasma cytokine levels, and clinical parameters of OA (erythrocyte sedimentation rate [ESR] and the Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) were analyzed using the Spearman correlation test. Results The percentages of total, CD8αα, and CD8αβ MAIT cells were higher in patients with OA compared to healthy controls. The percentages of total and CD8αα MAIT cells were higher in patients with multi-joint OA (MOA) compared to patients with knee-only OA (KOA). Plasma IFN-γ and TNF-α levels were elevated in patients with OA compared to healthy controls, and there was a positive correlation between plasma IFN-γ levels and the percentages of total, CD8αα, and CD8αβ MAIT cells. Plasma IFN-γ and IL-17 levels were higher in patients with MOA compared to healthy controls or patients with KOA. There were positive correlations between the percentages of total and CD8αα MAIT cells and clinical parameters (ESR and WOMAC scores) in patients with OA or MOA. Binary logistic regression analysis shown the frequency of MAIT cells was associated with the risk of OA. Conclusions MAIT cells and their subpopulations were significantly increased in patients with OA and have potential as biological markers of OA disease severity, especially in patients with MOA.

scholarly journals Modulation of Cytokine Release in Ex Vivo-Stimulated Blood from Borreliosis Patients

2001 ◽  
Vol 69 (2) ◽  
pp. 687-694 ◽  
Author(s):  
Isabel Diterich ◽  
Luc Härter ◽  
Dieter Hassler ◽  
Albrecht Wendel ◽  
Thomas Hartung
Keyword(s):  
Ex Vivo ◽  
Interleukin 10 ◽  
Cytokine Response ◽  
Healthy Controls ◽  
Cytokine Release ◽  
Necrosis Factor Alpha ◽  
Cell Counts ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT In lipopolysaccharide-stimulated blood from 71 late-stage borreliosis patients, the ex vivo cytokine release capacity of tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) was reduced to 28% ± 5% and to 31% ± 5% (P ≤ 0.001), respectively, compared to that of 24 healthy controls. White blood cell counts were normal in both groups. To investigate direct interactions between the pathogen and the immune cells, blood from healthy controls was exposed in vitro to live or heat-killedBorrelia or to Borrelia lysate. Compared to the pattern induced by bacterial endotoxins, a reduced release of TNF-α and IFN-γ and an enhanced secretion of interleukin-10 and granulocyte colony-stimulating factor was found. In blood from 10 borreliosis patients stimulated with Borrelia lysate, TNF-α formation was decreased to 31% ± 14% and IFN-γ formation was decreased to 8% ± 3% (P ≤ 0.001) compared to the cytokine response of blood from healthy controls (n = 24). We propose to consider anti-inflammatory changes in the blood cytokine response capacity elicited by Borrelia as a condition that might favor the persistence of the spirochete.

scholarly journals Experimental Endotoxemia Induces Leukocyte Adherence and Plasma Extravasation Within the Rat Pial Microcirculation

2011 ◽  
pp. 853-859 ◽  
Author(s):  
J. ZHOU ◽  
M. SCHMIDT ◽  
B. JOHNSTON ◽  
F. WILFART ◽  
S. WHYNOT ◽  
...  
Keyword(s):  
Intravital Microscopy ◽  
Plasma Extravasation ◽  
Plasma Cytokine ◽  
Experimental Endotoxemia ◽  
Cranial Window ◽  
Pial Vessels ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Ifn Γ ◽  
The Brain

Disturbance of capillary perfusions due to leukocyte adhesion, disseminated intravascular coagulation, tissue edema is critical components in the pathophysiology of sepsis. Alterations in brain microcirculation during sepsis are not clearly understood. The aim of this study is to gain an improved understanding of alterations through direct visualization of brain microcirculations in an experimental endotoxemia using intravital microscopy (IVM). Endotoxemia was induced in Lewis rats with Lipopolysaccharide (LPS, 15 mg/kg i.v.). The dura mater was removed via a cranial window to expose the pial vessels on the brain surface. Using fluorescence dyes, plasma extravasation of pial venous vessels and leukocyte-endothelial interaction were visualized by intravital microscopy 4 h after LPS administration. Plasma cytokine levels of IL1-β, IL-6, IFN-γ, TNF-α and KC/GRO were evaluated after IVM. A significant plasma extravasation of the pial venous vessels was found in endotoxemia rats compared to control animals. In addition, a significantly increased number of leukocytes adherent to the pial venous endothelium was observed in septic animals. Endotoxemia also induced a significant elevation of plasma cytokine levels of IL1-β, IL-6, IFN-γ, TNF-α and KC/GRO. Endotoxemia increased permeability in the brain pial vessels accompanied by an increase of leukocyte-endothelium interactions and an increase of inflammatory cytokines in the plasma.

CD4+CD25- effector T cells from healthy controls and MS patients do not differ in mRNA expression of IFN-γ, IL-2, and TNF-α

2004 ◽  
Vol 31 (S 1) ◽  
Author(s):  
A Hug ◽  
J Haas ◽  
A Viehöver ◽  
B Fritz ◽  
B Storch-Hagenlocher ◽  
...  
Keyword(s):  
T Cells ◽  
Mrna Expression ◽  
Effector T Cells ◽  
Healthy Controls ◽  
Tnf Α ◽  
Ifn Γ

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 The Initial Course of IL1β, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α with Regard to Severity Grade in Acute Pancreatitis

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 591
Author(s):  
Hanna Sternby ◽  
Hannes Hartman ◽  
Henrik Thorlacius ◽  
Sara Regnér
Keyword(s):  
Acute Pancreatitis ◽  
Roc Analysis ◽  
Paired Comparison ◽  
Severe Disease ◽  
Temporal Development ◽  
Predictive Capacity ◽  
Mean Values ◽  
Tnf Α ◽  
Significant Difference ◽  
Ifn Γ

Clinical reports on early immune dysregulation in acute pancreatitis (AP) are scarce. Herein we investigate the initial temporal development of selected biomarkers. Blood samples were taken at 0–24 and 25–48 h after onsets of AP were acquired. Mean values and temporal intermediate difference (delta-values) of IL-1β, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α were calculated. Differences between severity groups, predictive capacity of the biomarkers and association with severe disease were analyzed. Paired comparison of samples (n = 115) taken at 0–24 and 25–48 h after onsets of AP showed a change over time for IL-1β, IL-6, IL-8 and IL-10 (p < 0.05) and a significant difference between severity groups after 24 h. In ROC-analysis an IL-6 cut-off level of 196.6 pg/mL could differentiate severe AP (sensitivity 81.9, specificity 91.3). The delta-values of IL-1β and IL-6 were significantly associated with severe outcomes (odds ratios 1.085 and 1.002, respectively). Data of this work demonstrate a distinct change in IL-1β, IL-8, IL-10 and IL-6 over the first 48 h after onset of AP. The temporal development of biomarkers can assist in the early stratification of the disease. Herein IL-1β and IL-6 were associated with severe disease, however the prognostic capacity of investigated biomarkers is low.

scholarly journals Phenotypic and Functional Alterations of Immune Effectors in Periodontitis; A Multifactorial and Complex Oral Disease

2021 ◽  
Vol 10 (4) ◽  
pp. 875
Author(s):  
Kawaljit Kaur ◽  
Shahram Vaziri ◽  
Marcela Romero-Reyes ◽  
Avina Paranjpe ◽  
Anahid Jewett
Keyword(s):  
Periodontal Disease ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Oral Disease ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Tnf Α ◽  
Blood Mononuclear Cells ◽  
Ifn Γ ◽  
And Function

Survival and function of immune subsets in the oral blood, peripheral blood and gingival tissues of patients with periodontal disease and healthy controls were assessed. NK and CD8 + T cells within the oral blood mononuclear cells (OBMCs) expressed significantly higher levels of CD69 in patients with periodontal disease compared to those from healthy controls. Similarly, TNF-α release was higher from oral blood of patients with periodontal disease when compared to healthy controls. Increased activation induced cell death of peripheral blood mononuclear cells (PBMCs) but not OBMCs from patients with periodontal disease was observed when compared to those from healthy individuals. Unlike those from healthy individuals, OBMC-derived supernatants from periodontitis patients exhibited decreased ability to induce secretion of IFN-γ by allogeneic healthy PBMCs treated with IL-2, while they triggered significant levels of TNF-α, IL-1β and IL-6 by untreated PBMCs. Interaction of PBMCs, or NK cells with intact or NFκB knock down oral epithelial cells in the presence of a periodontal pathogen, F. nucleatum, significantly induced a number of pro-inflammatory cytokines including IFN-γ. These studies indicated that the relative numbers of immune subsets obtained from peripheral blood may not represent the composition of the immune cells in the oral environment, and that orally-derived immune effectors may differ in survival and function from those of peripheral blood.

scholarly journals Clearance of inflammatory cytokines in patients with septic acute kidney injury during renal replacement therapy using the EMiC2 filter (Clic-AKI study)

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Nuttha Lumlertgul ◽  
Anna Hall ◽  
Luigi Camporota ◽  
Siobhan Crichton ◽  
Marlies Ostermann
Keyword(s):  
Acute Kidney Injury ◽  
Growth Factor ◽  
Replacement Therapy ◽  
Kidney Injury ◽  
Final Analysis ◽  
Adsorptive Capacity ◽  
Clearance Rates ◽  
Plasma Cytokine ◽  
Tnf Α ◽  
Ifn Γ

Abstract Background The EMiC2 membrane is a medium cut-off haemofilter (45 kiloDalton). Little is known regarding its efficacy in eliminating medium-sized cytokines in sepsis. This study aimed to explore the effects of continuous veno-venous haemodialysis (CVVHD) using the EMiC2 filter on cytokine clearance. Methods This was a prospective observational study conducted in critically ill patients with sepsis and acute kidney injury requiring kidney replacement therapy. We measured concentrations of 12 cytokines [Interleukin (IL) IL-1β, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, vascular endothelial growth factor, monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF)] in plasma at baseline (T0) and pre- and post-dialyzer at 1, 6, 24, and 48 h after CVVHD initiation and in the effluent fluid at corresponding time points. Outcomes were the effluent and adsorptive clearance rates, mass balances, and changes in serial serum concentrations. Results Twelve patients were included in the final analysis. All cytokines except EGF concentrations declined over 48 h (p < 0.001). The effluent clearance rates were variable and ranged from negligible values for IL-2, IFN-γ, IL-1α, IL-1β, and EGF, to 19.0 ml/min for TNF-α. Negative or minimal adsorption was observed. The effluent and adsorptive clearance rates remained steady over time. The percentage of cytokine removal was low for most cytokines throughout the 48-h period. Conclusion EMiC2-CVVHD achieved modest removal of most cytokines and demonstrated small to no adsorptive capacity despite a decline in plasma cytokine concentrations. This suggests that changes in plasma cytokine concentrations may not be solely influenced by extracorporeal removal. Trial registration: NCT03231748, registered on 27th July 2017.

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