Adenosine and lymphocyte regulation

Adenosine is a potent extracellular messenger that is produced in high concentrations under metabolically unfavourable conditions. Tissue hypoxia, consequent to a compromised cellular energy status, is followed by the enhanced breakdown of ATP leading to the release of adenosine. Through the interaction with A2 and A3 membrane receptors, adenosine is devoted to the restoration of tissue homeostasis, acting as a retaliatory metabolite. Several aspects of the immune response have to be taken into consideration and even though in general it is very important to dampen inflammation, in some circumstances, such as the case of cancer, it is also necessary to increase the activity of immune cells against pathogens. Therefore, adenosine receptors that are defined as ‘sensors–of metabolic changes in the local tissue environment may be very important targets for modulation of immune responses and drugs devoted to regulating the adenosinergic system are promising in different clinical situations

P1 receptors and cytokine secretion

Evidence has accumulated in the last three decades to suggest tissue protection and regeneration by adenosine in multiple different cell types. Adenosine produced in hypoxic or inflamed environments reduces tissue injury and promotes repair by receptor-mediated mechanisms. Among other actions, regulation of cytokine production and secretion by immune cells, astrocytes and microglia (the brain immunocytes) has emerged as a main mechanism at the basis of adenosine effects in diseases characterized by a marked inflammatory component. Many recent studies have highlighted that signalling through A1 and A2A adenosine receptors can powerfully prevent the release of pro-inflammatory cytokines, thus inhibiting inflammation and reperfusion injury. However, the activation of adenosine receptors is not invariably protective of tissues, as signalling through the A2B adenosine receptor has been linked to pro-inflammatory actions which are, at least in part, mediated by increased release of pro-inflammatory cytokines from epithelial cells, astrocytes and fibroblasts. Here, we discuss the multiple actions of P1 receptors on cytokine secretion, by analyzing, in particular, the role of the various adenosine receptor subtypes, the complex reciprocal interplay between the adenosine and the cytokine systems, their pathophysiological significance and the potential of adenosine receptor ligands as new anti-inflammatory agents

Purinergic signalling and immune cells

This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells

Breastfeeding assessment score : systematic review and meta-analysis

BACKGROUND: Previous studies have revealed conflicting results for the Breastfeeding Assessment Score (BAS) in predicting early breastfeeding cessation. Our objective was to externally validate the BAS and provide summary accuracy estimates for this clinical prediction model. METHODS: We used the original data from a prospective cohort study. Additional studies were identified by searching electronic databases (Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane) from 2002 to 2013 and contacting research groups that had derived or validated the BAS. Prospective cohort studies were eligible if the BAS was computed at baseline and mothers were followed up for breastfeeding cessation. Two physicians extracted relevant information and independently assessed the methodological quality for the included studies. RESULTS: In the external validation cohort, 22 of 424 mothers (5.2%) discontinued breastfeeding within 14 days of infant age. The BAS predicted early breastfeeding cessation with an area under the curve of 0.70 (95% confidence interval [CI]: 0.65 to 0.74) and inadequate calibration. When restricting the meta-analysis to 3169 mother-infant pairs enrolled in 4 higher-quality studies, a BAS value <8 predicted early cessation with 0.80 sensitivity (95% CI: 0.69 to 0.91) and 0.51 specificity (95% CI: 0.32 to 0.70) summary estimates. CONCLUSIONS: Substantial between-study heterogeneity limited the interpretation of summary accuracy estimates. The BAS predicts early breastfeeding cessation with moderate accuracy, although local recalibration is advised before implementation. Further study is warranted to determine whether the BAS can help pediatricians in identifying mother-infant pairs that may benefit from more extensive breastfeeding assessment and support