Explore the vast range of titles available.

There is strong evidence for an association between major depressive disorder (MDD) and inflammation. However, some studies have not observed an increase in inflammatory cytokines in MDD, and the mechanism behind this is unknown. In the present study, we evaluated MDD severity using the Montgomery–Åsberg Depression Rating Scale (MADRS) and quantified mRNA levels of the blood inflammatory cytokines interleukin (IL) 1β, IL-6 and tumor necrosis factor alpha (TNF-α), as well as negative regulators of cytokine signaling—comprising IL-10, IL-1RA, SOCS1, SOCS2 and SOCS3—in MDD patients (n = 36), with a focus on mild MDD, and normal controls (NC, n = 30). We also measured the serum levels of IL-1β and IL-6. Neither the blood mRNA nor the protein levels of inflammatory cytokines were significantly elevated in the MDD group compared with the NC group. However, we observed significant decreases in SOCS1, SOCS2 and SOCS3 mRNA in the MDD group compared to the NC group. A significant finding was a decrease in SOCS3 mRNA after remission from MDD, suggesting that SOCS3 is a trait marker in depressive symptoms. We consider that our findings would be useful in elucidating the pathophysiological mechanism of depression.

A few experimental studies have shown the therapeutic effects of oxytocin on focal cerebral ischemia. In this study, the prophylactic effect of intranasal oxytocin on brain damage was investigated in a cerebral ischemic model. Intranasal oxytocin (8 IU/per mouse) was prescribed daily for one week. Cerebral ischemia was performed through bilateral common carotid artery occlusion (BCCAO) for 20 min and then blood flow was restored for 24 hr. Finally, neurological disorders, spatial learning and memory, neuronal death, and neuronal apoptosis were assessed in CA1, CA3, and dentate gyrus. Also, levels of interleukin-1β (IL-1β) and Tumor necrosis factor-alpha (TNFα) were measured in the hippocampus. Induction of global ischemia leads to neurological disorders and impairment of spatial learning and memory that are improved by pre-treatment with oxytocin ( <0.01). Cresyl violet staining showed that pretreatment with oxytocin significantly reduced the number of dead nerve cells in CA1, CA3, and dentate gyrus by 40.7, 32, and 34.3%, respectively. Also, positive TUNEL cells in CA1, CA3, and dental gyrus decreased by 15, 30, and 27%, respectively. In addition, levels of TNFα and IL-1β, which were extensively increased in ischemic mice, were significantly reduced with oxytocin pre-treatment. Pre-treatment of oxytocin reduces ischemic damage and improves neurological function and spatial memory. The neuroprotective effect of oxytocin is mediated by a decrease in cell death, apoptosis, and inflammatory mediators TNFα and IL-1β. Pre-treatment with oxytocin may be useful in people who are prone to stroke.

A ketogenic diet (KD) is known to have beneficial health effects. Various types of KD interventions have been applied to manage metabolic syndrome based on modification of diet parameters such as duration of intervention, macronutrient components, and total calories. Nevertheless, the beneficial health impact of isocaloric KD is largely unknown, especially in healthy subjects. The present study investigated the acute effects of a 3-day isocaloric KD. In this non-randomized intervention study, we recruited 15 healthy volunteers aged 24-38 years (7 men and 8 women) and placed them on an isocaloric KD restricting intake of carbohydrates but not energy (75% fat, 20% protein, 5% carbohydrate) for 3 days. Biochemical profiles and laboratory measurements were performed. Peripheral blood monocular cells were cultured, and measured cell stimulated cytokines. After short-term isocaloric KD, subjects lost body weight and serum free fatty acid levels were increased. These results accompanied elevated serum β-hydroxybutyrate (BHB) concentration and fibroblast growth factor 21 (FGF21) levels and improved insulin sensitivity. Regarding the direct effect of BHB on inflammasome activation, interleukin-1β (IL-1β) and tumor necrosis factor-α secretion in response to adenosine triphosphate or palmitate stimulation in human macrophages decreased significantly after isocaloric KD. In ex-vivo experiments with macrophages, both FGF21 and BHB further reduced IL-1β secretion compared to either BHB or FGF21 alone. The inhibitory effect of FGF21 on IL-1β secretion was blunted with bafilomycin treatment, which blocked autophagy flux. In conclusion, isocaloric KD for 3 days is a promising approach to improve metabolic and inflammatory status.

Background Interleukin-1β (IL-1β) is important mediator of inflammatory-induced suppression of reproductive axis at the hypothalamic level. At the beginning of inflammation, the main source of cytokines in the cerebrospinal fluid (CSF) is peripheral circulation, while over time, cytokines produced in the brain are more important. Melatonin has been shown to decrease pro-inflammatory cytokines concentration in the brain. In ewes, melatonin is used to advance the onset of a breading season. Little is known about CSF concentration of IL-1β in ewes and its correlation with plasma during inflammation as well as melatonin action on the concentration of IL-1β in blood plasma and the CSF, and brain barriers permeability in early stage of lipopolysaccharide (LPS)-induced inflammation. Methods Systemic inflammation was induced through LPS administration in melatonin- and sham-implanted ewes. Blood and CSF samples were collected before and after LPS administration and IL-1β and albumin concentration were measured. To assess the functions of brain barriers albumin quotient (QAlb) was used. Expression of IL-1β ( Il1B) and its receptor type I ( Il1r1 ) and type II ( Il1r2 ) and matrix metalloproteinase ( Mmp ) 3 and 9 was evaluated in the choroid plexus (CP). Results Before LPS administration, IL-1β was on the level of 62.0 ± 29.7 pg/mL and 66.4 ± 32.1 pg/mL in plasma and 26.2 ± 5.4 pg/mL and 21.3 ± 8.7 pg/mL in the CSF in sham- and melatonin-implanted group, respectively. Following LPS it increased to 159.3 ± 53.1 pg/mL and 197.8 ± 42.8 pg/mL in plasma and 129.8 ± 54.2 pg/mL and 139.6 ± 51.5 pg/mL in the CSF. No correlations was found between plasma and CSF IL-1β concentration after LPS in both groups. The QAlb calculated before LPS and 6 h after was similar in all groups. Melatonin did not affected mRNA expression of Il1B , Il1r1 and Il1r2 in the CP. The mRNA expression of Mmp3 and Mmp9 was not detected. Conclusions The lack of correlation between plasma and CSF IL-1β concentration indicates that at the beginning of inflammation the local synthesis of IL-1β in the CP is an important source of IL-1β in the CSF. Melatonin from slow-release implants does not affect IL-1β concentration in plasma and CSF in early stage of systemic inflammation.

Background—In the lipopolysaccharide (LPS) stimulated peripheral blood monocyte, the precursor form of interleukin 1β (IL-1β, 31 kD) is processed by IL-1β converting enzyme (ICE) to the mature, bioactive form (17 kD). IL-1β is a proinflammatory cytokine which is likely to have a role in the pathogenesis of inflammatory bowel disease (IBD). Aims—To investigate the expression and processing of IL-1β and ICE by tissue macrophages from normal and IBD colonic mucosa. Methods—Mucosal biopsy specimens and lamina propria cells from normal and IBD colons were studied by reverse transcription polymerase chain reaction (RT-PCR), western blot analysis, and ELISA (enzyme linked immunosorbent assay). Results—Normal colonic macrophages synthesised only the precursor form of IL-1β whereas in IBD the mature form was also produced. Similarly, cells from normal colonic mucosa synthesised ICE as the precursor (p45) only, whereas macrophages from IBD colons produced active (p20) ICE. Ac-Tyr-Val-Ala-Asp-CHO, a specific peptide aldehyde inhibitor of ICE, significantly reduced the amount of mature IL-1β released by isolated IBD macrophages (from a median of 1.2 (range 0.78–4.42) ng/ml to 0.43 (0.21–1.6) ng/ml; p<0.01). Conclusions—Exposure of normal colonic macrophages to LPS only induces the production of the precursor form of IL-1β, because the cells fail to activate ICE. In contrast, IBD colonic macrophages are able to activate ICE and hence release mature IL-1β in a manner similar to circulating monocytes. This is consistent with IBD macrophages being recently recruited from the circulating monocyte population. Targeted inhibition of ICE may represent a novel form of therapy in IBD.

Chronic low-grade inflammation is an important aspect of morbidity and mortality in older adults. The level of circulating pro-inflammatory cytokines (interleukin (IL)-6, tumor necrosis factor (TNF) or IL-1β) is a risk factor in cardiovascular and neurodegenerative diseases and is also associated with sarcopenia and frailties. The objective of this study was to assess each cytokine: IL-6, TNF, and IL-1β separately in the elderly with comorbidities against controls without diseases according to the data published in the available literature. The electronic bibliographic PubMed database was systematically searched to select all the relevant studies published up to July 2023. The total number of the subjects involved in the meta-analysis included patients with diseases ( =8154) and controls ( =33967). The overall concentration of IL-6 was found to be higher in patients with diseases compared to controls and the difference was statistically significant, with a -value of <0.001 (SMD, 0.16; 95% CI, 0.12-0.19). The heterogeneity was considerable with Q = 109.97 (P <0.0001) and I = 79.2%. The potential diagnostic usefulness of IL-6 was confirmed by odds ratio (OR) analysis (OR: 1.03, 95% CI (1.01; 1.05), =0.0029). The concentration of both TNF and IL-1β was elevated in the control group compared to patients and amounted to SMD -0.03; 95% CI, -0.09-0.02, -value 0.533 and SMD-0.29; 95% CI, -0.47- -0.12; = 0.001, respectively. For TNF, however, the difference was statistically insignificant. IL-6, unlike TNF and IL-1β, could be a useful and convenient marker of peripheral inflammation in older adults with various comorbidities.

Rosmarinic acid (RosA) is a water‐soluble polyphenol, which can be isolated from many herbs such as orthosiphon diffuses and rosmarinus officinalis. Previous studies have shown that RosA possesses various biological properties. In this study, we investigate the anti‐osteoarthritic effects of RosA in rat articular chondrocytes. Chondrocytes were pre‐treated with RosA, followed by the stimulation of IL‐1β. Real‐time PCR and Western blot were performed to detect the expression of matrix metalloproteinase (MMP)‐1, MMP‐3 and MMP‐13. Nitric oxide and PGE2 production were measured by Griess reagent and enzyme‐linked immunosorbent assay (ELISA). The expression of mitogen‐activated protein kinase (MAPK) and nuclear factor‐κB (NF‐κB) was also investigated by Western blot analysis. We found that RosA down‐regulated the MMPs expression as well as nitric oxide and PGE2 production in IL‐1β‐induced chondrocytes. In addition, RosA inhibited p38 and JNK phosphorylation as well as p65 translocation. The results suggest that RosA may be considered a possible agent in the treatment of OA.

BACKGROUND Interleukin (IL) 1β converting enzyme (now known as caspase 1) is able to process pro-IL-1β into its active form and is involved in proapoptotic signalling. AIMS To characterise IL-1 and caspase 1 expression in human colonic epithelial cells. METHODS Intracellular IL-1 content (IL-1α and IL-1β) was measured by ELISA in freshly isolated human normal colonocytes. Caspase 1 expression was determined both at the mRNA level using in situ hybridisation and reverse transcription polymerase chain reaction, and at the protein level by immunoblotting experiments using antibodies specific for the proform of caspase 1 and for its cleavage forms. RESULTS Low amounts of IL-1β were found in nearly all preparations (92%), and IL-1α was detected in only 45% of human colonocyte preparations. The normal colonic epithelium strongly expressed caspase 1, both at the mRNA level and at the protein level in its latent form. In contrast, caspase 1 was not expressed in colon cancer (primary colonic adenocarcinomas and cancer cell lines). CONCLUSIONS The demonstration that the human colonic epithelial barrier is able to express caspase 1 and its substrate IL-1β reinforces the concept that, under certain conditions, the epithelium could trigger an inflammatory reaction. In addition, the finding that caspase 1 was downregulated in colonic adenocarcinomas supports the concept that disrupted apoptosis pathways may be involved in tumour formation and/or may confer resistance to treatment.

Introduction The stress response is different in various individuals, however, the mechanisms that could explain these distinct effects are not well known and the molecular correlates have been considered one at the time. Particular harmful conditions occur if the subject, instead to cope the stressful events, succumb to them, in this case, a cascade reaction happens that through different signaling causes a specific reaction named “sickness behaviour.” The aim of this article is to review the complex relations among important molecules belonging to Central nervous system (CNS), immune system (IS), and endocrine system (ES) during the chronic stress response. Methods After having verified the state of art concerning the function of cortisol, norepinephrine (NE), interleukin (IL)‐1β and melatonin, we describe as they work together. Results We propose a speculative hypothesis concerning the complex interplay of these signaling molecules during chronic stress, highlighting the role of IL‐1β as main biomarker of this effects, indeed, during chronic stress its increment transforms this inflammatory signal into a nervous signal (NE), in turn, this uses the ES (melatonin and cortisol) to counterbalance again IL‐1β. During cortisol resistance, a vicious loop occurs that increments all mediators, unbalancing IS, ES, and CNS networks. This IL‐1β increase would occur above all when the individual succumbs to stressful events, showing the Sickness Behaviour Symptoms. IL‐1β might, through melatonin and vice versa, determine sleep disorders too. Conclusion The molecular links here outlined could explain how stress plays a role in etiopathogenesis of several diseases through this complex interplay. Central nervous system (CNS), immune system (IS), and endocrine system (ES) operate together during the chronic stress response. We propose that this complex molecular network is altered in sickness behaviors.

The tumor microenvironment (TME) plays key roles in promoting disease progression in the aggressive triple-negative subtype of breast cancer (TNBC; Basal/Basal-like). Here, we took an integrative approach and determined the impact of tumor-stroma-inflammation networks on pro-metastatic phenotypes in TNBC. With the TCGA dataset we found that the pro-inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β), as well as their target pro-metastatic chemokines CXCL8 (IL-8), CCL2 (MCP-1), and CCL5 (RANTES) were expressed at significantly higher levels in basal patients than luminal-A patients. Then, we found that TNFα- or IL-1β-stimulated co-cultures of TNBC cells (MDA-MB-231, MDA-MB-468, BT-549) with mesenchymal stem cells (MSCs) expressed significantly higher levels of CXCL8 compared to non-stimulated co-cultures or each cell type alone, with or without cytokine stimulation. CXCL8 was also up-regulated in TNBC co-cultures with breast cancer-associated fibroblasts (CAFs) derived from patients. CCL2 and CCL5 also reached the highest expression levels in TNFα/IL-1β-stimulated TNBC:MSC/CAF co-cultures. The elevations in CXCL8 and CCL2 expression partly depended on direct physical contacts between the tumor cells and the MSCs/CAFs, whereas CCL5 up-regulation was entirely dependent on cell-to-cell contacts. Supernatants of TNFα-stimulated TNBC:MSC \"Contact\" co-cultures induced robust endothelial cell migration and sprouting. TNBC cells co-cultured with MSCs and TNFα gained migration-related morphology and potent migratory properties; they also became more invasive when co-cultured with MSCs/CAFs in the presence of TNFα. Using siRNA to CXCL8, we found that CXCL8 was significantly involved in mediating the pro-metastatic activities gained by TNFα-stimulated TNBC:MSC \"Contact\" co-cultures: angiogenesis, migration-related morphology of the tumor cells, as well as cancer cell migration and invasion. Importantly, TNFα stimulation of TNBC:MSC \"Contact\" co-cultures has increased the aggressiveness of the tumor cells , leading to higher incidence of mice with lung metastases than non-stimulated TNBC:MSC co-cultures. Similar tumor-stromal-inflammation networks established in-culture with luminal-A cells demonstrated less effective or differently-active pro-metastatic functions than those of TNBC cells. Overall, our studies identify novel tumor-stroma-inflammation networks that may promote TNBC aggressiveness by increasing the pro-malignancy potential of the TME and of the tumor cells themselves, and reveal key roles for CXCL8 in mediating these metastasis-promoting activities.