Timing of Cervico-Vaginal Cytokine Collection during Pregnancy and Preterm Birth: A Comparative Analysis in the PRINCESA Cohort

Preterm birth (PTB), defined as birth before 37 completed weeks of gestation, is a major cause of infant morbidity and mortality. Inflammation is an important component in the physiopathologic pathway leading to PTB but results from cross-sectional studies on associations between inflammation, as measured by cytokines, and PTB are inconsistent. Timing of cytokine measurement during pregnancy varies between studies and may contribute to inconsistent findings. We investigated the effects of timing on associations between 16 cervico-vaginal cytokines (Eotaxin, IL-10, IL-12p40, IL-17, IL-1RA, sIL-2rα, IL-1a, IL-1β, IL-2, IL-6, IP-10, MCP-1, MIP-1α, MIP-1β, TNFα, and VEGF) and PTB among 90 women throughout pregnancy. We used logistic regression to compare associations between concentrations of cervico-vaginal cytokines from periods in pregnancy and PTB. Trimester 1 cytokines had the strongest positive associations with PTB; for example, OR = 1.76 (95% confidence interval: 1.28, 2.42) for IL-6. Second and third trimester associations were weaker but largely positive. IL-1α was the only cytokine with a negative association (trimesters 2, 3 and overall pregnancy). Strong first trimester associations between cytokines and PTB suggest that measuring cytokines early in pregnancy may hold promise for early identification of PTB risk. Variations in cytokine measurement during pregnancy may contribute to inconsistencies among studies.

Variability in the Laboratory Measurement of Cytokines

Context.— The measurement of cytokines in clinical laboratories is becoming an increasingly routine part of immune monitoring when administering biologic and cell-based immunotherapies and also for clinical assessment of inflammatory conditions. While a number of commercial assays and platforms are available for cytokine measurement, there is currently little standardization among these analytical methods. Objective.— To characterize the variability and comparability among cytokine testing platforms that are commonly used in clinical laboratories. Design.— We analyzed data for 4 cytokines (interleukin [IL]-1, IL-6, IL-8, and tumor necrosis factor-alpha [TNF-α]) from 6 College of American Pathologists cytokine surveys administered from 2015 to 2018. Analyses interrogated variability between testing methods and variability within each laboratory across the mailings. Results.— Significant variability was noted across methods with analysis of IL-1 showing the least variability and IL-6, IL-8, and TNF-α varying between methods to a greater extent. Intralab variability was also significant with TNF-α measurements again showing the greatest variability. Conclusions.— This retrospective analysis of College of American Pathologists proficiency testing data for cytokine measurement is the largest method comparison to date, and this study provides a description of the variation of cytokine measurement across methods, across laboratories, and within laboratories. Serial monitoring of cytokines should preferentially be performed by the same method within the same laboratory.

Cytokines profile of mice infected by high and low virulences of Indonesian T. evansi isolates

<p>Surra in livestock is caused by Trypanosoma evansi, a homoflagella blood protozoa that circulate in extracellular. This disease is widespread in Asia, Africa, South and Central America. According to the immunological aspect, the severity of surra in livestock and mice which infected by trypanosoma is associated with an inflammatory response. On the other hand, the survival time of mice depends on the regulation of Th1 synthesis and proinflammatory cytokines such as IFN-γ and TNF-α. The aim of this study was to observe the responses of proinflammatory cytokines IFN γ, TNF-α and anti-inflammatory IL-10 which result from interaction with parasites. This information is needed for improvements in the management of prevention of Surra in animals. A total of 30 mice were divided into 3 groups. The group was infected with a low virulency T. evansi (Pml287); high virulence (Bang87) respectively and one group was not infected as control. Mice sera were collected in every 4 days for cytokine measurement using an Enzyme Link-Immunosorbent Assay (ELISA). The result showed a difference response of proinflammatory and antiinflammation cytokine profile between the infected mice by isolates Bang 87 and Pml 287. Early deaths in mice infected by Bang 87 isolate were suspected as a result of the response of systemic inflammation syndromes characterized by elevated IFN-γ levels that were not adequately compensated by anti-inflammatory. Anemia contributes to the cause of death in mice that support multiple organ failures (multiple organ disfunction).</p>

miR-10b-5p is a novel Th17 regulator present in Th17 cells from ankylosing spondylitis

ObjectiveTo determine the microRNA (miR) signature in ankylosing spondylitis (AS) T helper (Th)17 cells.MethodsInterleukin (IL)-17A-producing CD4+ T cells from patients with AS and healthy controls were FACS-sorted for miR sequencing and qPCR validation. miR-10b function was determined by miR mimic expression followed by cytokine measurement, transcriptome analysis, qPCR and luciferase assays.ResultsAS Th17 cells exhibited a miR signature characterised by upregulation of miR-155-5p, miR-210-3p and miR-10b. miR-10b has not been described previously in Th17 cells and was selected for further characterisation. miR-10b is transiently induced in in vitro differentiated Th17 cells. Transcriptome, qPCR and luciferase assays suggest that MAP3K7 is targeted by miR-10b. Both miR-10b overexpression and MAP3K7 silencing inhibited production of IL-17A by both total CD4 and differentiating Th17 cells.ConclusionsAS Th17 cells have a specific miR signature and upregulate miR-10b in vitro. Our data suggest that miR-10b is upregulated by proinflammatory cytokines and may act as a feedback loop to suppress IL-17A by targeting MAP3K7. miR-10b is a potential therapeutic candidate to suppress pathogenic Th17 cell function in patients with AS.