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Aims. To investigate the effect of GLP-1/GLP-1R on the polarization of macrophages in the occurrence and development of atherosclerosis. Methods. Totally, 49 patients with coronary heart disease (CHD) and 52 cases of health control (HC) were recruited, all subjects accept coronary angiography gold standard inspection. One or more major coronary arteries (LM, LAD, LCx, and RCA) stenosis degree in 50% of patients as CHD group; the rest of the stenosis less than 50% or not seen obvious stenosis are assigned to the HC group. Flow cytometry were used to detect the percentage of (CD14+) M macrophages, (CD14+CD80+) M1 macrophages, (CD14+CD206+) M2 macrophages, and their surface GLP-1R expression differences in the two groups, using BD cytokine kit to detect the levels of IL-8, IL-1β, IL-6, IL-10, TNF, and IL-12p70. Results. GLP-1R expression on the surface of total macrophages and M2 macrophages was different between the CHD group and the HC group (P<0.05). There was no difference in the percentage of total, M1 or M2 macrophages (P>0.05). Concentration of IL-8 in the HC group was higher than that in the CHD group (P<0.05). There is no significant difference in the cytokine IL-1β, IL-6, IL-10, TNF, and IL-12p70 in the two groups (P>0.05). After controlling for potential confounders including age, gender, smoking status (S.S.), drinking status (D.S.), HR, SBP, DBP, PP, TC, TG, HDL-C, LDL-C, GHbA1c, M, M1, M2, GLP-1R_M, GLP-1R_M1, GLP-1R_M2, IL-8, IL-1β, IL-6, IL-10, TNF, and IL-12p70 by multiple linear regression, decreasing Gensini Score was significantly associated with increased percentage of M1 macrophage. Conclusion. GLP-1R agonist is independent of the hypoglycemic effect of T2DM and has protective effect on cardiovascular system. GLP-1R may regulate the polarization of macrophages toward M2, thus playing a protective role in the progression of coronary atherosclerosis.

IL-10, IL-6, and TNF-α: Central factors in the altered cytokine network of uremia—The good, the bad, and the ugly. It has been increasingly apparent that wasting and cardiovascular disease (CVD) is associated with a persistent systemic inflammatory response in end-stage renal disease (ESRD) patients. The reasons for the increased risk of inflammation in ESRD patients appear to be complex, including nondialysis as well as dialysis-related factors. The combination of an impaired immune response coupled with persistent immune stimulation may have a role in the low-grade systemic inflammation and altered cytokine balance that characterizes the uremic state and which may translate into increased risk for vascular disease. The accelerated atherosclerotic process of ESRD may involve several interrelated processes, such as oxidative stress, endothelial dysfunction, and vascular calcification, in a milieu of constant low-grade inflammation with impaired function of neutrophils and T cells, as well as a dysregulated cytokine network. Although a large number of pro- and anti-inflammatory cytokines are of importance, available data suggest that the anti-inflammatory cytokine interleukin (IL)-10 and the mainly proinflammatory cytokines IL-6 and tumor necrosis factor-α (TNF-α) may play important roles in the development of Th imbalance, CVD and wasting in the uremic milieu. Given the strong association between proinflammatory cytokines and complications common in ESRD, such as vascular calcification and wasting, the potential role of both general and targeted anticytokine treatment strategies in ESRD patients needs further evaluation.

The Class 2 alpha-helical cytokines consist of interleukin-10 (IL-10), IL-19, IL-20, IL-22, IL-24 (Mda-7), and IL-26, interferons (IFN-alpha, -beta, -epsilon, -kappa, -omega, -delta, -tau, and -gamma) and interferon-like molecules (limitin, IL-28A, IL-28B, and IL-29). The interaction of these cytokines with their specific receptor molecules initiates a broad and varied array of signals that induce cellular antiviral states, modulate inflammatory responses, inhibit or stimulate cell growth, produce or inhibit apoptosis, and affect many immune mechanisms. The information derived from crystal structures and molecular evolution has led to progress in the analysis of the molecular mechanisms initiating their biological activities. These cytokines have significant roles in a variety of pathophysiological processes as well as in regulation of the immune system. Further investigation of these critical intercellular signaling molecules will provide important information to enable these proteins to be used more extensively in therapy for a variety of diseases.

Thymic stromal lymphopoietin (TSLP) is overtly expressed on skin lesions of atopic dermatitis (AD), and the initiative role of TSLP-activated DCs in AD has gained much attention in the past few years, while its actions on other immune cells such as T cells have been given less notice. We aimed to clarify whether TSLP receptor (TSLPR) is expressed on certain populations of T cells and whether TSLP possesses the capability to directly interact with T cells from AD patients. Peripheral lymphocytes from 51AD patients are analyzed by flow cytometry, and ex vivo experiments using peripheral blood and lesional skin-derived T cells were conducted. TSLPR expression was defined to CD4+ T cells, and CD4+CCR4+CXCR3−CCR7−CCR10+CLA+ T cells in AD patients exhibited enhanced TSLPR expression. The frequency of TSLPR+CD4+ T cells correlated with disease activity. CD4+ T cells from AD patients directly interacted with TSLP to produce a higher amount of IL-4 than those from normal subjects, and this action was attenuated with anti-TSLPR antibody. The importance of IL-4 in the induction of TSLPR expression was found in AD T cells. Our findings indicate that T cells from AD patients possess strong potential to directly interact with TSLP to promote Th2 response.

Cytokine storm, a life-threatening disorder involving cytokine elevations and immune-cell hyperactivation, has various causes and is characterized by constitutional symptoms, systemic inflammation, and multiorgan dysfunction. Selective interventions can ameliorate the illness.

Ischemic stroke is one of the leading causes of morbidity and mortality globally. Hundreds of clinical trials have proven ineffective in bringing forth a definitive and effective treatment for ischemic stroke, except a myopic class of thrombolytic drugs. That, too, has little to do with treating long-term post-stroke disabilities. These studies proposed diverse options to treat stroke, ranging from neurotropic interpolation to venting antioxidant activity, from blocking specific receptors to obstructing functional capacity of ion channels, and more recently the utilization of neuroprotective substances. However, state of the art knowledge suggests that more pragmatic focus in finding effective therapeutic remedy for stroke might be targeting intricate intracellular signaling pathways of the ‘neuroinflammatory triangle’: ROS burst, inflammatory cytokines, and BBB disruption. Experimental evidence reviewed here supports the notion that allowing neuroprotective mechanisms to advance, while limiting neuroinflammatory cascades, will help confine post-stroke damage and disabilities.

Hematopoiesis is the cumulative result of intricately regulated signaling pathways that are mediated by cytokines and their receptors. Proper culmination of these diverse pathways forms the basis for an orderly generation of different cell types. Recent studies conducted over the past 10–15 years have revealed that hematopoietic cytokine receptor signaling is largely mediated by a family of tyrosine kinases termed Janus kinases (JAKs) and their downstream transcription factors termed STATs (signal transducers and activators of transcription). Aberration in these pathways, such as that caused by the recently identified JAK2V617F mutation, is an underlying cause for diseases such as leukemias and other myeloproliferative disorders. This recent discovery, when coupled with the fact that STATs are activated by oncoproteins such as BCR-ABL, underscores the importance of the JAK-STAT pathway in both normal cellular development and disease states.

Key Points Common cytokine receptor γ-chain (γc) cytokines control the immune response at overlapping, as well as distinct, checkpoints, and the levels of expression of γc-cytokine receptors are differentially regulated during an immune response. Interleukin-2 (IL-2), IL-7 and IL-15 exert diverse effects related to T-cell survival, activation and clonal expansion, and memory-cell development and maintenance. IL-7 mediates the survival of naive and memory T cells. Memory T-cell homeostasis can be affected by secondary encounter with antigen, bystander proliferation or attrition. IL-15 is essential for the homeostatic proliferation of memory CD8 + T cells and maintenance of the steady-state level of CD8 + T-cell memory. IL-15 might exert direct effects on memory CD8 + T cells or might act on other cell types, which subsequently regulate memory T-cell proliferation. IL-15 might also be presented by other cells to CD8 + T cells through interaction with the IL-15 receptor β-chain. Evidence has accumulated that cytokines have a fundamental role in the differentiation of memory T cells. Here, we follow the CD8 + T cell from initial activation to memory-cell generation, indicating the checkpoints at which cytokines determine the fate of the T cell. Members of the common cytokine-receptor γ-chain (γc)-cytokine family — in particular, interleukin-7 (IL-7) and IL-15 — act at each stage of the immune response to promote proliferation and survival. In this manner, a stable and protective, long-lived memory CD8 + T-cell pool can be propagated and maintained.

BackgroundCytokines are key regulators of measles vaccine humoral and cellular immunity. Single-nucleotide polymorphisms (SNPs) that are associated with differences in cytokine levels should also influence measles vaccine–induced immunity MethodsWe genotyped 118 measles-mumps-rubella–vaccinated subjects for SNPs from 6 cytokine genes (interleukin [IL]–2, IL-4, IL-10, IL-12A, IL-12B, and interferon [IFN]–γ) and their receptors (IL-2RA, IL-2RB, IL-4RA, IL-10RA, IL-10RB, IL-12RB1, IL-12RB2, and IFN-γR). Associations of SNPs with measles-specific antibodies, lymphoproliferation, and secreted cytokines were determined using χ2 tests and analyses of covariance ResultsWe found significant associations (P<.05) between SNPs in the IL-2, IL-10, and IL-12RB genes and measles vaccine–induced immunity. The IVS1-100G (rs2069762) and the Ex2-34G (rs2069763) SNPs within the IL-2 gene were associated with high antibody and high lymphoproliferative responses, whereas SNPs within the IL-10 and IL-12R genes were associated with low antibody and lymphoproliferative responses to measles. SNPs within the IL-4RA and IL-12B genes varied significantly (P<.05) across immune response measures. Significant associations were also found between SNPs and secreted cytokine levels ConclusionsSpecific SNPs in the cytokine and cytokine receptor genes are significantly associated with variations in measures of the immune response to measles vaccination. These results need to be further validated in a larger cohort

Interactions between the immune system and the nervous system have been described mostly in the context of diseases. More recent studies have begun to reveal how certain immune cell-derived soluble effectors, the cytokines, can influence host behaviour even in the absence of infection. In this Review, we contemplate how the immune system shapes nervous system function and how it controls the manifestation of host behaviour. Interactions between these two highly complex systems are discussed here also in the context of evolution, as both may have evolved to maximize an organism’s ability to respond to environmental threats in order to survive. We describe how the immune system relays information to the nervous system and how cytokine signalling occurs in neurons. We also speculate on how the brain may be hardwired to receive and process information from the immune system. Finally, we propose a unified theory depicting a co-evolution of the immune system and host behaviour in response to the evolutionary pressure of pathogens.In this Review, Kipnis and colleagues explain how signals from the immune system can shape host behavioural responses, even in the absence of infection or disease. In particular, the authors focus on the cytokine pathways that modulate behavioural responses and consider the evolutionary basis of these neuroimmune interactions.