Plasma cytokenes quantification among Trypanosoma brucei rhodesiense sleeping sickness cases and controls in Rumphi, Malawi

IntroductionTrypanosoma brucei (T.b.) rhodesiense is the cause of the acute form of human African trypanosomiasis (HAT) in eastern and southern African countries, including Malawi. For a long time, untreated HAT infections were believed to be 100% fatal. However, recent studies show that infection by T.b. rhodesiense can result in a wide range of clinical outcomes in its human host. Apart from other factors such as parasite diversity, cytokines have been strongly implicated to play a major role in the outcome of T.b. rhodesiense infections. In this study, we quantify the levels of three cytokines Interleukin-8 (IL-8), Tumor Necrotic Factor alpha (TNF-α) and Interleukin -10 (IL-10) in plasma amongst HAT cases (treated and untreated) and controls recruited during medical survey. MethodsTwo-hundred and thirty-three plasma samples (HAT cases and controls) from Rumphi, one of the endemic areas in Malawi were used. Blood collected was centrifuged, plasma extracted and stored in cryovials at -800 C until processing. Plasma cytokine concentration was measured using ELISA. ResultsPlasma samples for 233 individuals, 76 HAT cases and 157 controls were quantified. Among the cases, nine had their plasma collected before treatment (untreated) and the rest were treated before blood for plasma analysis was collected. Controls had significantly higher mean plasmatic levels of TNF-α (94.5 ±474.12 pg/ml) and IL-8 (2258.6 ±5227.4 pg/ml) than cases TNF-α (29.35±181.58 pg/ml) and IL-8 (1191.3±4236.09 pg/ml). Controls and cases had similar mean levels of IL-10 in plasma. Only IL-8 had statistically significant higher median levels in the untreated than treated HAT cases P=0.006.ConclusionOur data suggest that cytokines could be considered as biomarkers of HAT infection and treatment. Further studies with a larger cohort of cases and additional cytokines which are known to be associated with HAT infection outcomes will be required to evaluate these cytokines further.

An exploratory study demonstrating that salivary cytokine profiles are altered in children with small area thermal injury

Serum can be used to investigate changes in cytokine concentration following burn injury in children, however for children receiving treatment in an outpatient setting, blood is not routinely collected and therefore cannot be used for monitoring. The aim of this study was to investigate the use of saliva as a non-invasive tool for predicting burn outcomes by measuring the concentration of salivary cytokines in children with small area burns. A multiplex cytokine assay was used to measure 17 cytokines in the saliva of paediatric patients with burns (n = 20) and healthy controls (n = 20). After the removal of cytokines that had >30% of samples below the assay lower detection limit, six cytokines including IL-1β, IL-4, IL-7, IL-8, MCP-1 and TNFα were analysed for association with burns. IL-1β and IL-4 were found to be significantly elevated in the paediatric burn patients compared to healthy controls. Interestingly, IL-1β was also significantly elevated in scald burns, compared to contact burns. In addition, biologically meaningful differences in cytokine concentration were identified in patients with different burn characteristics, which warrant further investigation. This exploratory study provides evidence that cytokines can be detected in the saliva of children and that salivary cytokine profiles differ between healthy controls and children with burns. Overall, this study demonstrates the value of saliva for the investigation of cytokines and its potential application in paediatric diagnostics, specifically in situations where blood collection is not appropriate.

Ivacaftor partially corrects airway inflammation in a humanized G551D rat

Animal models have been highly informative for understanding the pathogenesis and progression of cystic fibrosis (CF) lung disease. In particular, the CF rat models recently developed have addressed mechanistic causes of the airway mucus defect characteristic of CF, and how these may change when CFTR activity is restored using new modulator therapies. We hypothesized that inflammatory changes to the airway would develop spontaneously and progressively, and that these changes would be resolved with modulator therapy. To test this, we used a humanized-CFTR rat expressing the G551D variant that responds to the CFTR modulator ivacaftor. Markers typically found in the CF lung were assessed, including neutrophil influx, small airway histopathology, and inflammatory cytokine concentration. Young hG551D rats did not express inflammatory cytokines at baseline but did upregulate these in response to inflammatory trigger. As the hG551D rats aged, histopathology worsened, accompanied by neutrophil influx into the airway and increasing concentrations of TNF-α, IL-1α, and IL-6 in the airways. Ivacaftor administration reduced concentrations of these cytokines when administered to the rats at baseline but was less effective in the rats that had also received inflammatory stimulus. Therefore, we conclude that administration of ivacaftor resulted in an incomplete resolution of inflammation when rats received an external trigger, suggesting that CFTR activation may not be enough to resolve inflammation in the lungs of patients with CF.

Immune Responses after Heavy Alcohol Consumption: Cytokine Concentrations in Hangover-Sensitive and Hangover-Resistant Drinkers

This study investigated immunological changes during an alcohol hangover, and the possible difference between hangover-resistant and hangover-sensitive drinkers in terms of immune reactivity. Using a semi-naturalistic design, N = 36 healthy social drinkers (18 to 30 years old) provided saliva samples on a control day (after drinking no alcohol) and on a post-alcohol day. Hangover severity was rated directly after saliva collection. Cytokine concentrations, interleukin (IL)-1β, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α, and hangover severity were compared between both test days and between hangover-sensitive and -resistant drinkers. Data from N = 35 drinkers (17 hangover-sensitive and 18 hangover-resistant) were included in the statistical analyses. Relative to the control day, there were significant increases in saliva IL-6 and IL-10 concentrations on the post-alcohol day. No significant differences in cytokine concentrations were found between hangover-sensitive and hangover-resistant drinkers, nor did any change in cytokine concentration correlate significantly with hangover severity. In line with previous controlled studies assessing cytokines in blood, the current naturalistic study using saliva samples also demonstrated that the immune system responds to high-level alcohol intake. However, further research is warranted, as, in contrast to previous findings in blood samples, changes in saliva cytokine concentrations did not differ significantly between hangover-sensitive and hangover-resistant drinkers, nor did they correlate significantly with hangover severity.

Analysis of IL-1β, CXCL8, and TNF-α levels in the crevicular fluid of patients with periodontitis or healthy implants

Background Our study aimed to assess the level of IL-1β, CXCL8, and TNF-α in peri-implant sulcular fluid (PISF) collected from patients with no clinical symptoms of mucositis or peri-implantitis and compare them with cytokine concentration in gingival crevicular fluid (GCF) acquired from patients with healthy periodontium and those with varying severity of periodontitis. Methods A total of 189 subjects were included in the study, and GCF/PISF samples were checked for IL-1β, CXCL8, and TNF-α levels using an ELISA test. Results The IL-1β level in PISF in patients with implants was significantly lower than in GCF in patients with mild, moderate, or severe periodontitis. The CXCL8 level in PISF was considerably lower than in patients with moderate periodontitis. The TNF-α level in PISF in patients with implants was markedly higher compared to subjects with healthy periodontium or patients with mild periodontitis. Conclusion Analysis of cytokine levels may help describe the pathogenesis and early diagnosis of peri-implantitis and prevision in high-risk patients.

Effect of non-encapsulated and encapsulated active dried yeast on blood cell count, blood metabolites and immune response of finishing beef heifers

A study was conducted to evaluate whether encapsulated active dried yeast (EDY), compared with non-protected (ADY) or antibiotics (ANT), improved immune response and blood metabolites of finishing beef heifers. Blood urea nitrogen was lower (P ˂ 0.05) with supplemented ADY and mixture of ADY and EDY (MDY) compared with control. Supplementation of MDY mixture also resulted in lower (P ˂ 0.05) red blood cell distribution width than control. Lipopolysaccharide binding protein was less (P ˂ 0.05) for EDY than control, ANT and ADY as well as cytokine concentration of interleukin-6 was less (P ˂ 0.05) for MDY versus control.

Analysis of IL-1β, CXCL8, and TNF-α levels in the crevicular fluid of patients with periodontitis or healthy implants

Background: Our study aimed to assess the level of IL-1β, CXCL8, and TNF-α in peri-implant sulcular fluid (PISF) collected from patients with no clinical symptoms of mucositis or peri-implantitis and compare them with cytokine concentration in gingival crevicular fluid (GCF) acquired from patients with healthy periodontium and those with varying severity of periodontitis. Methods: A total of 189 subjects were included in the study, and GCF/PISF samples were checked for IL-1β, CXCL8, and TNF-α levels using an ELISA test.Results: The IL-1β level in PISF in patients with implants was significantly lower than in GCF in patients with mild, moderate, or severe periodontitis. The CXCL8 level in PISF was considerably lower than in patients with moderate periodontitis. The TNF-α level in PISF in patients with implants was markedly higher compared to subjects with healthy periodontium or patients with mild periodontitis. Conclusion: Analysis of cytokine levels may help describe the pathogenesis and early diagnosis of peri-implantitis and prevision in high-risk patients.

A DNA origami-based aptamer nanoarray for potent and reversible anticoagulation in hemodialysis

Effective and safe hemodialysis is essential for patients with acute kidney injury and chronic renal failures. However, the development of effective anticoagulant agents with safe antidotes for use during hemodialysis has proven challenging. Here, we describe DNA origami-based assemblies that enable the inhibition of thrombin activity and thrombus formation. Two different thrombin-binding aptamers decorated DNA origami initiates protein recognition and inhibition, exhibiting enhanced anticoagulation in human plasma, fresh whole blood and a murine model. In a dialyzer-containing extracorporeal circuit that mimicked clinical hemodialysis, the origami-based aptamer nanoarray effectively prevented thrombosis formation. Oligonucleotides containing sequences complementary to the thrombin-binding aptamers can efficiently neutralize the anticoagulant effects. The nanoarray is safe and immunologically inert in healthy mice, eliciting no detectable changes in liver and kidney functions or serum cytokine concentration. This DNA origami-based nanoagent represents a promising anticoagulant platform for the hemodialysis treatment of renal diseases.

Analysis of IL-1β, CXCL8, and TNF-α levels in the crevicular fluid of patients with periodontitis or healthy implants

Background: Our study aimed to assess the level of IL-1β, CXCL8, and TNF-α in peri-implant sulcular fluid (PISF) collected from patients with no clinical symptoms of mucositis or peri-implantitis and compare them with cytokine concentration in gingival crevicular fluid (GCF) acquired from patients with healthy periodontium and those with varying severity of periodontitis. Methods: A total of 189 subjects were included in the study, and GCF/PISF samples were checked for IL-1β, CXCL8, and TNF-α levels using an ELISA test.Results: The IL-1β level in PISF in patients with implants was significantly lower than in GCF in patients with mild, moderate, or severe periodontitis. The CXCL8 level in PISF was considerably lower than in patients with moderate periodontitis. The TNF-α level in PISF in patients with implants was markedly higher compared to subjects with healthy periodontium or patients with mild periodontitis. Conclusion: Analysis of cytokine levels may help describe the pathogenesis and early diagnosis of peri-implantitis and prevision in high-risk patients.

Limbic Encephalitis Brain Damage Induced by Cocal Virus in Adult Mice Is Reduced by Environmental Enrichment: Neuropathological and Behavioral Studies

We previously demonstrated, using the Piry virus model, that environmental enrichment promotes higher T-cell infiltration, fewer microglial changes, and faster central nervous system (CNS) virus clearance in adult mice. However, little is known about disease progression, behavioral changes, CNS cytokine concentration, and neuropathology in limbic encephalitis in experimental models. Using Cocal virus, we infected C57Bl6 adult mice and studied the neuroanatomical distribution of viral antigens in correlation with the microglial morphological response, measured the CNS cytokine concentration, and assessed behavioral changes. C57Bl6 adult mice were maintained in an impoverished environment (IE) or enriched environment (EE) for four months and then subjected to the open field test. Afterwards, an equal volume of normal or virus-infected brain homogenate was nasally instilled. The brains were processed to detect viral antigens and microglial morphological changes using selective immunolabeling. We demonstrated earlier significant weight loss and higher mortality in IE mice. Additionally, behavioral analysis revealed a significant influence of the environment on locomotor and exploratory activity that was associated with less neuroinvasion and a reduced microglial response. Thus, environmental enrichment was associated with a more effective immune response in a mouse model of limbic encephalitis, allowing faster viral clearance/decreased viral dissemination, reduced disease progression, and less CNS damage.