Transfer Of Cytokines Research Articles

Recent advances and future avenues in understanding the role of adipose tissue cross talk in mediating skeletal muscle mass and function with ageing

Sarcopenia, broadly defined as the age-related decline in skeletal muscle mass, quality, and function, is associated with chronic low-grade inflammation and an increased likelihood of adverse health outcomes. The regulation of skeletal muscle mass with ageing is complex and necessitates a delicate balance between muscle protein synthesis and degradation. The secretion and transfer of cytokines, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), both discretely and within extracellular vesicles, have emerged as important communication channels between tissues. Some of these factors have been implicated in regulating skeletal muscle mass, function, and pathologies and may be perturbed by excessive adiposity. Indeed, adipose tissue participates in a broad spectrum of inter-organ communication and obesity promotes the accumulation of macrophages, cellular senescence, and the production and secretion of pro-inflammatory factors. Pertinently, age-related sarcopenia has been reported to be more prevalent in obesity; however, such effects are confounded by comorbidities and physical activity level. In this review, we provide evidence that adiposity may exacerbate age-related sarcopenia and outline some emerging concepts of adipose-skeletal muscle communication including the secretion and processing of novel myokines and adipokines and the role of extracellular vesicles in mediating inter-tissue cross talk via lncRNAs and miRNAs in the context of sarcopenia, ageing, and obesity. Further research using advances in proteomics, transcriptomics, and techniques to investigate extracellular vesicles, with an emphasis on translational, longitudinal human studies, is required to better understand the physiological significance of these factors, the impact of obesity upon them, and their potential as therapeutic targets in combating muscle wasting.

The exosomes in tumor immunity

Exosomes are a kind of nanometric membrane vesicles and can be released by almost all kinds of cells, including cancer cells. As the important mediators in intercellular communications, exosomes mediate exchange of protein and genetic material derived from parental cells. Emerging evidences show that exosomes secreted by either host cells or cancer cells are involved in tumor initiation, growth, invasion and metastasis. Moreover, communications between immune cells and cancer cells via exosomes play dual roles in modulating tumor immunity. In this review, we focus on exosome-mediated immunosuppression via inhibition of antitumor responses elicited by immune cells (DCs, NK cells, CD4+ and CD8+ T cells, etc.) and induction of immunosuppressive or regulatory cell populations (MDSCs, Tregs and Bregs). Transfer of cytokines, microRNAs (miRNAs) and functional mRNAs by tumor-derived exosomes (TEXs) is crucial in the immune escape. Furthermore, exosomes secreted from several kinds of immune cells (DCs, CD4+ and CD8+ Tregs) also participate in immunosuppression. On the other hand, we summarize the current application of DC-derived and modified tumor-derived exosomes as tumor vaccines. The potential challenges about exosome-based vaccines for clinical application are also discussed.

Cytokine Concentration in Foals’ Serum Pre‐ and Post Suckling

Reasons for performing studyColostrum acts as a source of immunomodulatory molecules for the neonate. Little information is available about the transfer of cytokines via colostrum in the foal.ObjectivesTo investigate the transfer via colostrum of IL‐4, IL‐13, IL‐8 and IFN‐γ.Study designProspective observational study.MethodsJugular venous blood pre‐ (T0) and post suckling (T24) and colostrum were collected from 14 healthy foals and their dams. The cytokines’ concentration was measured with an ELISA test. Serum IgG concentration was measured in foals at T24 with an immunoturbidimetric assay. Since data were not normally distributed, nonparametric tests for statistical analysis were used. The Wilcoxon t test evaluated the difference in each cytokine concentration between T0 and T24. Spearman rank correlation tested the association between cytokines’ concentration in T24 serum and in colostrum, between T24–T0 (ΔT) serum concentration and colostrum concentration, and between cytokines serum concentration at T24 and IgG concentration.ResultsAll the foals had a complete transfer of passive immunity. A statistically significant difference was found between serum IL‐4 concentration at T0 and at T24. The significant correlations found were: serum IL‐4 concentration at T24 with IL‐4 concentration in colostrum, serum IL‐13 concentration at T24 with IgG serum concentration, and IL‐4 concentration in colostrum with ΔT serum IL‐4 concentration.ConclusionsThe results support the hypothesis that IL‐4 is transferred via colostrum to the foal, as reported for TNF‐α [1]. The presence of IL‐8 in the foal's serum at T0 suggests an endogenous production. The IL‐13 concentration is close to zero for the major part of serum and colostrum samples suggesting a subject‐dependent immunologic response. The IFN‐γ is present both in colostrum and in T0 serum suggesting that foals are not deficient at birth.Ethical animal reasearch: Studies approved by the Ethical Committee of the Faculty of Veterinary Medicine, University of Bologna. Oral informed consent was given by the owners. Sources of funding: University of Bologna. Competing interests: None.

Transfer of Proinflammatory Cytokines Across Term Placenta

Increased concentrations of proinflammatory cytokines in amniotic fluid indicate the presence of intra-amniotic inflammation and increase the risk of preterm birth, cerebral palsy, and bronchopulmonary dysplasia. The purpose of this study was to find out if the proinflammatory cytokines, tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6, transfer across the placenta, and thereby determine whether intra-amniotic inflammatory response, measured from the amniotic fluid, is of maternal or fetal origin. Nineteen placentas from healthy women undergoing elective cesarean delivery at term with intact membranes and without labor, were dually perfused ex vivo in an open circulation system for either 30 minutes or 2 hours. Tumor necrosis factor-alpha, IL-1beta, and IL-6 were added to maternal or fetal circulation in a concentration usually found in chorioamnionitis. As a reference, placentas without added cytokine were also perfused. The concentrations of cytokines were determined by enzyme immunoassays (enzyme-linked immunosorbent assay [ELISA]). After the addition of the cytokine to the arterial perfusate, the venous concentration on the same side of the placenta increased rapidly and reached a plateau at 10 minutes. No transfer of any cytokine in either direction was detected. Some endogenous release of IL-6 was observed in response to the perfusion. Proinflammatory cytokines do not cross normal term placenta.

Transfer of cytokines through human fetal membranes

Intact human fetal membranes (amnion, chorion and decidua) were incubated with 125I-labelled cytokines added to the fetal or maternal sides of the membrane. The transfer of 125I-labelled interleukin-6 (IL-6), 125I-labelled tumour necrosis factor alpha (TNF-alpha), 125I-labelled interleukin-1 alpha (IL-1 alpha) and 125I-labelled interleukin-1 beta (IL-1 beta) was determined by measurement of radioactivity in a gamma counter and the integrity of the cytokines was assessed by acid precipitation and by radioimmunoassay. IL-1 alpha and IL-1 beta were transferred through human fetal membranes in both feto-maternal and materno-fetal directions at similar rates. Only 2-4% of the cytokine originally added appeared to be intact on the opposing side of the membrane after 24 h of culture. Transfer of intact TNF-alpha (5-7%) and IL-6 (8-17%) was greater than that of the IL-1 isomers. Low but variable amounts of the four cytokines tested may be transferred through the human fetal membrane. This finding suggested that concentrations of cytokines in amniotic fluid would not reflect those produced by decidua if the fetal membranes are intact.

Transfer of cytokines through human fetal membranes.

Intact human fetal membranes (amnion, chorion and decidua) were incubated with 125I-labelled cytokines added to the fetal or maternal sides of the membrane. The transfer of 125I-labelled interleukin-6 (IL-6), 125I-labelled tumour necrosis factor alpha (TNF-alpha), 125I-labelled interleukin-1 alpha (IL-1 alpha) and 125I-labelled interleukin-1 beta (IL-1 beta) was determined by measurement of radioactivity in a gamma counter and the integrity of the cytokines was assessed by acid precipitation and by radioimmunoassay. IL-1 alpha and IL-1 beta were transferred through human fetal membranes in both feto-maternal and materno-fetal directions at similar rates. Only 2-4% of the cytokine originally added appeared to be intact on the opposing side of the membrane after 24 h of culture. Transfer of intact TNF-alpha (5-7%) and IL-6 (8-17%) was greater than that of the IL-1 isomers. Low but variable amounts of the four cytokines tested may be transferred through the human fetal membrane. This finding suggested that concentrations of cytokines in amniotic fluid would not reflect those produced by decidua if the fetal membranes are intact.