serum cytokines
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2022 ◽  
Vol 422 ◽  
pp. 126963
Author(s):  
Miao Liu ◽  
Lei Zhao ◽  
Linlin Liu ◽  
Wenting Guo ◽  
Huihua Yang ◽  
...  

2021 ◽  
Author(s):  
Jay Peters ◽  
Diego Jose Maselli ◽  
Mandeep Mangat ◽  
Jacqueline J. Coalson ◽  
Cecilia Hinojosa ◽  
...  

Rationale Mycobacterium avium complex, is the most common nontuberculous mycobacterial respiratory pathogen in humans. Disease mechanisms are poorly understood due to the absence of a reliable animal model for M. avium complex pulmonary disease. Objectives Assess the susceptibility, immunologic and histopathologic responses of the common marmoset ( Callithrix jacchus ) to M. avium complex pulmonary infection. Methods 7 adult female marmosets underwent endobronchial inoculation with 10 8 colonyforming units of M. intracellulare and were monitored for 30 or 60 days. Prior to infection, chest radiograph and serum cytokines were assessed; serum cytokines were also monitored weekly for 30 days. At sacrifice 30 days (3 animals) or 60 days (4 animals) after infection, chest radiograph, serum and bronchoalveolar lavage cytokines, histopathology, and cultures of the bronchoalveolar lavage, lungs, liver, and kidney were analyzed. Measurements and Main Results Five of seven animals (two at 30 days and three at 60 days of infection) had positive lung cultures for M. intracellulare . Extra-pulmonary cultures were positive in three animals. All animals appeared healthy throughout the study. All five animals with positive lung cultures had radiographic changes consistent with pneumonitis. At 30 days, those with M. intracellulare lung infection showed granulomatous inflammation while at 60 days there was less inflammatory change but bronchiectasis was noted. The cytokine response in the bronchoalveolar lavage fluid was uniformly greater in the animals with positive M. intracellulare cultures than those without a productive infection with greater levels at 30-days compared to 60-days. Similarly, serum cytokines were more elevated in the animals that had positive M. intracellulare cultures compared to those without a productive infection, peaking 14-21 days after inoculation. Conclusion Endobronchial instillation of M. intracellulare resulted in pulmonary mycobacterial infection in marmosets with a differential immune response, radiographic and histopathologic abnormalities, and an indolent course consistent with M. avium complex lung infection in humans.


2021 ◽  
Vol 157 (10) ◽  
pp. 464-472
Author(s):  
Joanna Krajewska Wojciechowska ◽  
Wojciech Krajewski ◽  
Katarzyna Kościelska-Kasprzak ◽  
Tomasz Zatoński

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S51-S52
Author(s):  
Zhaohui Xu ◽  
Rebecca M Glowinski ◽  
Shira H Cohen ◽  
Cameron Mertz ◽  
Sara Mertz ◽  
...  

Abstract Background Almost 4 million children have tested positive for Coronavirus Disease 2019 (COVID-19) as of June 3 2021, representing 14% of all cases in USA. Children present with diverse clinical findings including the multisystem inflammatory syndrome in children (MIS-C). In this study, we measured serum cytokine concentrations in children with COVID-19 to identify differences in immune profiles according to clinical presentations. Methods A total of 133 children 0-21 years of age with COVID-19 were enrolled at Nationwide Children’s Hospital, in Columbus, Ohio. Nasopharyngeal swab RT-PCR testing was used for SARS-CoV-2 detection and quantification. Clinical and laboratory information were obtained, and blood samples were collected for measurement of cytokines with a 92-plex inflammation assay (Olink). Normalized cytokine expression levels in patients were compared with serum samples from 66 pre-pandemic age-matched healthy controls. Results COVID-19 children included: 1) those identified by universal screening (n=47); 2) moderate disease (ward; n=48); 3) severe disease (PICU; n=20); 4) MIS-C (n=18). Children identified by universal screening were hospitalized for trauma, appendicitis or new onset diabetes among others. Children with symptomatic COVID-19 had significantly higher SARS-CoV-2 viral loads than children with MIS-C or those identified via universal screening. Concentrations of interferon (IFN) related cytokines (IFNg, CXCL9, CXCL10, CXCL11), interleukins (IL6, IL8, IL10, IL17A, IL18, IL24) and other inflammatory cytokines (TGF, TNF, VEGF, MCP, CD40) were significantly increased in children with acute COVID-19 and MIS-C compared with children identified by universal screening and healthy controls. These cytokines were positively correlated with C-reactive protein, D-dimer and disease severity in COVID-19, but negatively correlated with viral loads (Fig 1). MIS-C showed stronger inflammatory response than acute COVID-19 (Fig 2). Correlation of Age-adjusted cytokine expression values with viral load, disease severity, CRP and D-dimer. Pearson correlation coefficient is shown for each pair. Red: positive correlation; blue: negative correlation Cytokines that differentiate MIS-C from acute COVID-19 Heatmap shows the differential expressed cytokines between MIS-C and acute severe COVID-19 (padj<0.05, FC>2). The age-adjusted expression values are normalized the median of healthy controls. Red: up-regulation, blue: down-regulation. Conclusion We identified three cytokine clusters in children with COVID-19 according to clinical presentations. Correlations of serum cytokines with clinical/laboratory parameters could be used to identify potential biomarkers associated with disease severity in COVID-19 Disclosures Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member)Sanofi (Advisor or Review Panel member) Octavio Ramilo, MD, Adagio (Consultant)Bill & Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support)Lilly (Consultant)Merck (Consultant, Grant/Research Support)NIH (Grant/Research Support)Pfizer (Consultant)SANOFI (Board Member)


2021 ◽  
Vol 73 (5) ◽  
Author(s):  
Renato DONFRANCESCO ◽  
Paola NATIVIO ◽  
Edoardo BORRELLI ◽  
Eleonora GIUA ◽  
Elda ANDRIOLA ◽  
...  

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A731-A731
Author(s):  
Christoph Huber ◽  
Guzman Alonso ◽  
Elena Gerralda ◽  
Christoph Bucher ◽  
Philippe Jacqmin ◽  
...  

BackgroundANV419 is a novel interleukin-2 (IL-2)/anti-IL-2 fusion protein with preferential signaling through the IL-2 beta/gamma receptor that induces selective proliferation of CD8 T cells and NK cells in vivo for the treatment of cancer. The safety and pharmacodynamic effects of ANV419 were studied in a 4-week cynomolgus monkey GLP study to support the ongoing PhI dose escalation clinical trial.MethodsANV419 was administered by i.v. injection over 1 min at doses of 0.03, 0.1, 0.3 mg/kg, or vehicle control on days 1 and 15 of the 29-day study. Assessments included body weight, blood pressure, hematology, clinical pathology, serum cytokines, immunophenotyping, histopathology, and pharmacokinetics.ResultsThe pharmacokinetics of ANV419 were characterized by target mediated disposition, with a half-life of approximately 24h at concentrations not affected by target mediated clearance. Dose-dependent increases in WBC were observed after each injection, driven by preferential expansion of CD8 T cells and NK cells over Tregs. NK cells were more sensitive to ANV419 than CD8 T cells reaching maximal proliferation in blood at 0.03 mg/kg vs. 0.3 mg/kg for CD8 T cells. Hematological changes included: transient dose-dependent increase in basophils; elevation in eosinophils, up to 2.2-fold above control animals at > 0.03 mg/kg, remaining within the normal range for cynomolgus monkeys (<1.94 G/L); minor decrease in platelets at day 4 after each injection. There were no relevant treatment-related changes in inflammatory serum cytokines (IL-1b, IL-5, IL-6, IL-8, IFNg, TNFa, GM-CSF). A mild systemic inflammatory response was observed at 0.3 mg/kg evidenced by a transient increase of CRP on days 4 and 19, preceded after the first injection by a slight dose dependent increase in IL-1RA at 4h post injection, and an increase in IL-10 at 24h post treatment at 0.3mg/kg. No significant changes in body weights or blood pressure and no signs of capillary leak were observed during the entire study.A multi-part PhI dose-escalation study of ANV419 has been initiated in cancer patients. In the part A single patient escalation cohort, two patients have been dosed Q2W multiple times with 0.003mg/kg and 0.006mg/kg respectively with the expected PD profile and no DLT observed.ConclusionsConsistent findings, relating to expected effects of ANV419 as a not-alpha IL-2 agonist, demonstrated a favorable tolerability and safety profile at pharmacodynamically relevant doses that strongly support its translational development in cancer patients to identify clinical benefits.


2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 273-274
Author(s):  
Alejandra V Ruiz ◽  
Liliana L Betancourt López

Abstract Plant extracts contain active molecules called pronutrients that could replace antibiotic growth promoters (AGP) in order to improve intestinal integrity, optimize feed utilization and consequently, increase productive performance. The purpose of this study was to evaluate the effect of a mixture of pronutrients on hematological parameters, serum cytokins regulation, intestinal morphology, organs weight and productive parameters. The trial was conducted with 480 one-day-old male broilers of the Ross AP 308 divided into 3 groups: Group CON - Basal diet only, Group AB supplemented with bacitracin methylene disalicylate and Halquinol continuously, and Group PR with a mixture powder of pronutrients, respectively. The experiment lasted up to the 35th day of age. 3 % of crude soybean was added to all basal diets as a challenge for intestinal integrity. All data were statistically analyzed using ANOVA and P value less than 0.05 was set as statistically significant and 0.05 &lt; P &lt; 0.1 as tendency. A decrease of all serum cytokines (IL-1β, IL-6, IL-8, IL-10) in supplemented broilers with pronutrients was observed. The intestinal morphology parameters were better (length and villi depth) and performance parameters such as feed intake, body weight and feed conversion rate (FCR) throughout the trial were improved in broilers supplemented with pronutrients (P &lt; 0.05). Dietary supplementation with a natural additive based on pronutrients demonstrated to be an effective alternative to AGP to improve intestinal morphology, productive performance and regulating hematological and immune values in broilers challenged with diets containing raw soybean.


Author(s):  
Elise S Bisset ◽  
Stefan Heinze-Milne ◽  
Scott A Grandy ◽  
Susan E Howlett

Abstract Aerobic exercise is a promising intervention to attenuate frailty, but preclinical studies have used only male animals. We investigated the impact of voluntary aerobic exercise on frailty, biological age (FRIGHT clock), predicted life expectancy (AFRAID clock) and mortality in both sexes and determined whether exercise was associated with changes in inflammation. Older (21-23 months) male (n=12) and female (n=22) C57Bl/6 mice matched for baseline frailty scores were randomized into exercise (running wheel) and sedentary (no wheel) groups. Frailty index scores were measured biweekly (13 weeks), and 23 serum cytokines were measured at midpoint and endpoint. Exercise levels varied between mice but not between the sexes. Exercise had no effect on mortality, but it attenuated the development of frailty in both sexes (female=0.32±0.04 vs 0.21±0.01; p=0.005; male=0.30±0.02 vs. 0.22±0.02; p=0.042) and reduced frailty in older females after 10 weeks. FRIGHT scores were unaffected by exercise but increased with time in sedentary males indicating increased biological age. Exercise prevented the age-associated decline in AFRAID scores in older females such that exercised females had a longer life expectancy. We investigated whether aerobic exercise was associated with changes in systemic inflammation. Cytokine levels were not affected by exercise in males, but levels of pro-inflammatory cytokines were positively correlated with the frequency of exercise in females. Despite increases in systemic inflammation, exercise reduced frailty and increased lifespan in older females. Thus, voluntary aerobic exercise, even late in life, has beneficial effects on health in both sexes but may be especially helpful in older females.


Author(s):  
Xiaohan Yang ◽  
Qiang Jia ◽  
Gongchang Yu ◽  
Bo Jiao ◽  
Kai Liu ◽  
...  

Abstract Objectives The present study aimed to investigate the distribution of lymphocyte subsets and cytokines expression in the peripheral blood of bitumen fumes-exposed workers. Methods In this study, 129 workers from molding and roasting workshops were recruited as the exposed group and 99 office and quality inspection staff were chosen as the control. The polycyclic aromatic hydrocarbons (PAHs) levels of bitumen fumes in individual and fixed-point air samples and the urinary levels of 1-hydroxypyrene (1-OH-P), 1-hydroxynaphthols (1-OH-N) and 2-hydroxynaphthols (2-OH-N) in workers were measured using High Performance Liquid Chromatography. The lymphocyte subsets and serum cytokines concentrations were analyzed by flow cytometry and cytometric bead array, respectively. Results The median values of PAHs were 0.08 mg/m3 for permissible concentration-time weighted average and 0.12 mg/m3 for permissible concentration-short term exposure (PC-STEL) in molding and roasting workshops, which were higher than that in the control area (&lt; 0.01 mg/m3). Multivariate linear regression models were used to adjust for influential covariates, including age, gender, work age, smoking status, and alcohol consumptions. After adjusting for these covariates, we compared levels of urinary PAHs metabolites, the percentages of lymphocyte subsets, and serum cytokines concentrations between the two groups. The 1-OH-P, 1-OH-N, and 2-OH-N levels in the urine of bitumen fumes exposed workers were significantly higher than that in the controls (P &lt; 0.05). Compared with the control group, the percentage of the natural killer (NK) cell (CD56+ cell) was significantly increased in the exposed group (P &lt; 0.001). There was a significant decrease in the percentages of CD3+ T cell, CD4+ T cell, and CD8+ T cell in the exposed group compared to the control (P &lt; 0.001). The serum levels of interleukin-1β (IL-1β) and IL-6 in bitumen fumes exposed workers were significantly higher than that of the controls (P &lt; 0.05). Moreover, positive correlations were observed between the serum levels of IL-1β, IL-6, and urinary 1-OH-P levels in bitumen fumes-exposed workers, respectively (P &lt; 0.05). There were no significant differences in the serum levels of IL-8, tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-1β (MIP-1β) and monocyte chemotactic protein-1 (MCP-1) between the exposed group and the control group (P &gt; 0.05). Conclusion Our study suggested that low dose of bitumen fumes exposure could decrease the percentage of T cell, increase the percentage of NK cell and stimulate the release of serum IL-1β and IL-6 in the peripheral blood of exposed workers. The serum levels of IL-1β and IL-6 were positive correlated with the urinary 1-OH-P levels in bitumen fumes exposed workers. These results may inform the search for potential effective biomarkers and provide evidences for early health monitoring in workers occupationally exposed to bitumen fumes.


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