Plasma Concentrations Of IL-1β Research Articles

IL1B Polymorphism (rs1143634) and IL-1β Plasma Concentration as Predictors of Nutritional Disorders and Prognostic Factors in Multiple Myeloma Patients.

Multiple myeloma (MM) is a hematological neoplasm of the early precursor of B-cells. The most characteristic symptoms observed during MM include hypocalcemia, anemia, bacterial infections, and renal damage. Nutritional disorders, especially malnutrition, are noted in about 35-71% of MM patients. Interleukin 1 beta (IL-1β) is a proinflammatory cytokine responsible for muscle atrophy and lipolysis during malnutrition and cachexia. This study aimed to evaluate the usefulness of the IL1B single-nucleotide polymorphism (SNP) (rs1143634) and plasma concentration of IL-1β in the assessment of the risk of nutritional disorders and prognosis in patients with MM. In our study, 93 patients with the de novo MM were enrolled. The real-time PCR with specific TaqMan probes method was used in genotyping. The IL-1β ELISA kit was used to determine IL-1β concentration in plasma samples. Patients with the CC genotype, compared to the carriers of the other variants of the IL1B, demonstrated significantly higher concentrations of IL-1β in plasma (7.56 vs. 4.97 pg/mL), a significantly higher risk of cachexia (OR = 5.11), and a significantly higher risk of death (HR = 2.03). Moreover, high IL-1β plasma level was related to a significantly higher risk of cachexia (OR = 7.76); however, it was not significantly associated with progression-free survival (PFS) or overall survival (OS). Determination of the IL1B SNP (rs1143634) and plasma concentration of IL-1β may be useful in the assessment of the risk of cachexia and prognosis in patients with MM.

Abstract 4989: Targeting IL-1β mitigates radiation induced MDSC expansion & improves survival in glioblastoma

Abstract Background: Our previous research demonstrated that radiation therapy (RT) for glioblastoma (GBM) induces aberrant myelopoiesis, increasing production of myeloid derived suppressor cells (MDSCs) and exacerbating T-cell suppression. However, the precise biological mechanisms underlying this phenomenon remain unclear. This study aims to elucidate the role of the pro-inflammatory cytokine interleukin-1beta (IL-1β) in RT-induced myelopoiesis and its correlation with poor prognosis in GBM patients. Methods: We conducted an extensive analysis of circulatory immune cells and pro-inflammatory cytokines in GBM patients treated with chemoradiotherapy. Using an orthotopic mouse model of GBM, we investigated the impact of IL-1β on myelopoiesis and survival. Functional assays were employed to examine MDSC expansion. Multi-color flow cytometry was used for immune profiling. Results: We found that RT elevated the plasma IL-1β concentration in both GBM patients and GBM-bearing mice, which also corresponded with an increase of MDSC in blood. In the murine GBM model, RT appeared to promote hematopoietic stem (HSPC) differentiation towards myelopoiesis. This led to increased MDSC precursor cells in the bone marrow, elevated circulating MDSCs in blood, and more infiltration of MDSCs in the tumor microenvironment (TME). Similar effects were observed in GBM-bearing mice following the administration of exogenous IL-1β. In contrast, inhibition of IL-1β using anti-IL-1β antibody during RT led to reduced myelopoiesis. When anti-IL-1β antibody was combined with functional inhibition of MDSCs using phosphodiesterase-5 inhibitor-tadalafil during RT, we observed decreased MDSC infiltration and increased CD8+ T cell infiltration in the TME. The combination approach also extended the survival of GBM-bearing mice after RT longer than either drug alone. Conclusions: Irradiation of GBM appears to induce IL-1β to promote aberrant myelopoiesis and MDSC expansion. A multi-pronged approach to inhibit MDSC production using IL-1β inhibitor and MDSC function using tadalafil during RT may be a promising approach to overcome the immune-suppressive TME of GBM. Citation Format: Subhajit Ghosh, Jiayi Huang, David DeNardo, Dennis Hallahan, Jerry Jaboin, Dinesh Thotala. Targeting IL-1β mitigates radiation induced MDSC expansion & improves survival in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4989.

Algorithm for predicting death in newborns with respiratory pathology and perinatal damage to the central nervous system on artificial ventilation

The objective was to predict the fatal outcome of the disease in newborns on artificial lung ventilation by means of an intelligent analysis of the immunological database.Materials and methods. The retrospective clinical study included 108 mature newborns. Upon admission to the intensive care unit, on the 3rdday and at the end of the disease, the plasma concentrations of IL-1β, IL-6, IL-8, TNF-α, G-CSF, s-Fas, FGF, NO were determined by ELISA; the relative content of CD3+CD19–, CD3–CD19+, CD3+CD4+, CD3+CD8+, CD69+, CD71+, CD95+, HLA-DR+, CD34+; CD14+, CD3–CD56+ by immunophenotyping; relative content of lymphocytes with expression of AnnexinV-FITC+PI–, AnnexinV-FITC+PI+. By the method of decision trees, the rule of predicting death was formulated.Results. The patient is predicted fatal outcome if, upon admission to intensive care, he has the relative content of lymphocytes with expression of AnnexinV-FITC+PI+ ≥ 0.95 % and plasma concentration of G-CSF ≤ 1.46 pg\ml or G-CSF ≥ 1.46 pg\ml and AnnexinV-FITC+PI+ ≥ 4.75 %(specificity 98.68 %; sensitivity 96.97 %; accuracy 98.68 %).Conclusion. In newborns with respiratory pathology and perinatal involvement of the central nervous system on artificial ventilation, death is determined by the high activity of T-lymphocyte apoptosis mediated by the low plasma concentration of granulocyte colony stimulating factor.

Antipyretic effects of Xiangqin Jiere granules on febrile young rats revealed by combining pharmacodynamics, metabolomics, network pharmacology, molecular biology experiments and molecular docking strategies

Xiangqin Jiere granules (XQJRG) is a proprietary Chinese medicine treating children’s colds and fevers, but its mechanism of action is unclear. The aim of this study was to explore the antipyretic mechanisms of XQJRG based on pharmacodynamics, non-targeted metabolomics, network pharmacology, molecular biology experiments, molecular docking, and molecular dynamics (MD) simulation. Firstly, the yeast-induced fever model was constructed in young rats to study antipyretic effect of XQJRG. Metabolomics and network pharmacology studies were performed to identify the key compounds, targets and pathways involved in the antipyretic of XQJRG. Subsequently, MetScape was used to jointly analyze targets from network pharmacology and metabolites from metabolomics. Finally, the key targets were validated by enzyme-linked immunosorbent assay (ELISA), and the affinity and stability of key ingredient and targets were evaluated by molecular docking and MD simulation. The animal experimental results showed that after XQJRG treatment, body temperature of febrile rats was significantly reduced, 13 metabolites were significantly modulated, and pathways of differential metabolite enrichment were mainly related to amino acid and lipid metabolism. Network pharmacology results indicated that quercetin and kaempferol were the key active components of XQJRG, TNF, AKT1, IL6, IL1B and PTGS2 were core targets. ELISA confirmed that XQJRG significantly reduced the plasma concentrations of IL-1β, IL-6, and TNF-α, and the hypothalamic concentrations of COX-2 and PGE2. Molecular docking demonstrated that the binding energies of kaempferol to the core targets were all below −5.0 kcal/mol. MD simulation results showed that the binding free energies of TNF-kaempferol, IL6-kaempferol, IL1B-kaempferol and PTGS2-kaempferol were −87.86 kcal/mol, −70.41 kcal/mol, −69.95 kcal/mol and −106.67 kcal/mol, respectively. In conclusion, XQJRG has antipyretic effects on yeast-induced fever in young rats, and its antipyretic mechanisms may be related to the inhibition of peripheral pyrogenic cytokines release by constituents such as kaempferol, the reduction of hypothalamic fever mediator production, and the amelioration of disturbances in amino acid and lipid metabolism. Communicated by Ramaswamy H. Sarma

Anti-Bordetella bronchiseptica effects of targeted bacteriophages via microbiome and metabolic mediated mechanisms

Bordetella bronchiseptica poses a significant challenge in the context of respiratory infections, particularly in weanling pigs. In this study, we investigated the impact of a novel targeted bacteriophage in controlling B. bronchiseptica challenge (BBC) in an experimental design involving five distinct treatment groups: NC (no challenge), PC (BBC challenge), BF (108 pfu bacteriophage/kg diet + BBC), BN (2 × 107 pfu/day bacteriophage by nasal spray + BBC), and AT (antibiotic + BBC). The experiment was conducted for 2 weeks. The highest turbinate score was observed in the PC. The BF treatment showed higher plasma IL (interleukine)-1β and IL-6 compared with the BN and AT treatments. Plasma concentrations of IL-1β were increased in the BF pigs compared with the BN, AT, and NC. Among the BBC groups, the PC treatment exhibited a higher abundance of Staphylococcus. aureus and B. bronchiseptica in the lung. A lower S. aureus, Streptococcus. suis, and B. bronchiseptica colonization was detected in the AT compared with the BF and BN treatments. The BF showed lower plasma zonulin compared with the BN and AT. A higher plasma concentration of superoxide dismutase was observed in the BF and AT compared with PC and BN. The BN influenced the glycine, serine-threonine metabolism; glycerolipid metabolism; glyoxylate-dicarboxylate metabolism; and arachidonic acid metabolism compared with the NC. In conclusion, nasal-sprayed bacteriophage effectively controlled B. bronchiseptica infection, however, their efficiency was lower than the antibiotic.

Fatigue, Toll-Like Receptor 4, and Pro-Inflammatory Cytokines in Adults With Subarachnoid Hemorrhage: A 6-Month Longitudinal Study.

Fatigue is prevalent in subarachnoid hemorrhage (SAH) survivors. Biological mechanisms underlying fatigue post-SAH are not clear. Inflammation may contribute to the development of fatigue. This study aimed to examine the associations between inflammatory markers and fatigue during the first 6months post-SAH. Specific biomarkers examined included both early and concurrent expression of Toll-Like Receptor 4 (TLR4) messenger RNA (mRNA) and plasma concentrations of pro-inflammatory cytokines, Tumor Necrosis Factor-alpha (TNF-α), Interleukin (IL)1β, and IL6. We conducted a 6-month longitudinal study with a convenience sample of 43 SAH survivors. We collected blood samples on days 2, 3, and 7 and 2, 3, and 6months post-SAH to assess biomarkers. Fatigue was assessed by the PROMIS Fatigue Scale at 2, 3, and 6months. Linear mixed models were used to test the associations between early (days 2, 3, and 7) and concurrent (2, 3, and 6months) TLR4 mRNA expression (TagMan gene expression assays) and TNF-α, IL1β, and IL6 plasma concentrations (multiplex assays) and concurrent fatigue. 28% of SAH survivors experienced fatigue during the first 6months post-SAH. Fatigue levels in SAH survivors were higher than those of the U.S. population and consistent during the 6months. Experience of fatigue during the 6months post-SAH was associated with higher IL1β plasma concentrations on day 7 and IL1β, IL6, and TNF-α plasma concentrations during the 6months post-SAH. Inflammation appears to underlie the development of fatigue in SAH survivors.

The role of dietary magnesium deficiency in inflammatory hypertension.

Nearly 30% of adults consume less than the estimated average daily requirement of magnesium (Mg2+), and commonly used medications, such as diuretics, promote Mg2+ deficiency. Higher serum Mg2+ levels, increased dietary Mg2+ in-take, and Mg2+ supplementation are each associated with lower blood pressure, suggesting that Mg2+-deficiency contributes to the pathogenesis of hypertension. Antigen-presenting cells, such as monocytes and dendritic cells, are well-known to be involved in the pathogenesis of hypertension. In these cells, processes implicated as necessary for increased blood pressure include activation of the NLRP3 inflammasome, IL-1β production, and oxidative modification of fatty acids such as arachidonic acid, forming isolevuglandins (IsoLGs). We hypothesized that increased blood pressure in response to dietary Mg2+-depletion leads to increased NLRP3, IL-1β, and IsoLG production in antigen presenting cells. We found that a Mg2+-depleted diet (0.01% Mg2+ diet) increased blood pressure in mice compared to mice fed a 0.08% Mg2+ diet. Mg2+-depleted mice did not exhibit an increase in total body fluid, as measured by quantitative magnetic resonance. Plasma IL-1β concentrations were increased (0.13 ± 0.02 pg/mL vs. 0.04 ± 0.02 pg/mL). Using flow cytometry, we observed increased NLRP3 and IL-1β expression in antigen-presenting cells from spleen, kidney, and aorta. We also observed increased IsoLG production in antigen-presenting cells from these organs. Primary culture of CD11c+ dendritic cells confirmed that low extracellular Mg2+ exerts a direct effect on these cells, stimulating IL-1β and IL-18 production. The present findings show that NLRP3 inflammasome activation and IsoLG-adduct formation are stimulated when dietary Mg2+ is depleted. Interventions and increased dietary Mg2+ consumption may prove beneficial in decreasing the prevalence of hypertension and cardiovascular disease.

Effect of supplementing live Saccharomyces cerevisiae yeast on performance, rumen function, and metabolism during the transition period in Holstein dairy cows

Dairy cows have to face several nutritional challenges during the transition period, and live yeast supplementation appears to be beneficial in modulating rumen activity. In this study, we evaluated the effects of live yeast supplementation on rumen function, milk production, and metabolic and inflammatory conditions. Ten Holstein multiparous cows received either live Saccharomyces cerevisiae (strain Sc47; SCY) supplementation from -21 to 21 d from calving (DFC) or a control diet without yeast supplementation. Feed intake, milk yield, and rumination time were monitored until 35 DFC, and rumen fluid, feces, milk, and blood samples were collected at different time points. Compared with the control diet, SCY had increased dry matter intake (16.7 vs. 19.1 ± 0.8 kg/d in wk 2 and 3) and rumination time postpartum (449 vs. 504 ± 19.9 min/d in wk 5). Milk yield tended to be greater in SCY (40.1 vs. 45.2 ± 1.7 kg/d in wk 5), protein content tended to be higher, and somatic cell count was lower. In rumen fluid, acetate molar proportion was higher and that of propionate lower at 21 DFC, resulting in increased acetate:propionate and (acetate + butyrate):propionate ratios. Cows in the SCY group had lower fecal dry matter but higher acetate and lower propionate proportions on total volatile fatty acids at 3 DFC. Plasma analysis revealed a lower degree of inflammation after calving in SCY (i.e., lower haptoglobin concentration at 1 and 3 DFC) and a likely better liver function, as suggested by the lower γ-glutamyl transferase, even though paraoxonase was lower at 28 DFC. Plasma IL-1β concentration tended to be higher in SCY, as well as Mg and P. Overall, SCY supplementation improved rumen and hindgut fermentation profiles, also resulting in higher dry matter intake and rumination time postpartum. Moreover, the postcalving inflammatory response was milder and liver function appeared to be better. Altogether, these effects also led to greater milk yield and reduced the risk of metabolic diseases.

Melatonin decreases IRF-3 protein expression in the gastrocnemius muscle, reduces IL-1β and LPS plasma concentrations, and improves the lipid profile in rats with apical periodontitis fed on a high-fat diet.

To evaluate the effects of melatonin (MEL) on the expression of toll-like receptor-4 (TLR4); myeloid differentiation primary response protein-88 (MyD88); TIR-domain-containing adapter-inducing interferon-β (TRIF); IFN regulatory-factor-3 (IRF-3); nuclear factor kappa-B (NF-κB); plasma concentrations of interleukin-1β (IL-1β) and lipopolysaccharide (LPS); and lipid profile of rats with apical periodontitis (AP) fed on a high-fat diet (HFD). Eighty 60-day-old rats were divided into eight groups: control, AP, HFD, HFDAP, CNMEL, APMEL, HFDMEL and HFDAPMEL. HFD groups were fed on a HFD for 107days. On day 7, experimental AP was induced in the AP groups, and after 70days, MEL (5mg/kg) was administered to the MEL groups for 30days. Plasma concentrations of LPS and IL-1β were analyzed using enzyme-linked immunosorbent assay, and the lipid profile was analyzed using biochemical tests. The expression of proteins involved in the TLR4 pathway (TLR4, MyD88, TRIF, IRF-3 and NF-κB) in the gastrocnemius muscle (GM) was evaluated using western blotting and qRT-PCR. Treatment with MEL decreased IRF-3 protein expression in GM and IL-1β plasma concentration in the APMEL and HFDMEL groups. Reduction in LPS plasma concentration was reported only in the HFDMEL group. Additionally, a decrease in LDL and an increase in HDL were observed in the HFDMEL and HFDAPMEL groups. Treatment with MEL exhibited anti-inflammatory and anti-hyperlipidemic effects attributed to HFD and AP by reducing the plasma concentrations of IL-1β and LPS in addition to reducing IRF-3 protein expression in the GM, which is associated with the production of inflammatory cytokines.

Abstract 10537: A Comparison of Endothelial Nitric Oxide Synthase(eNOS)-Based Platelet Subpopulation Ratios and Platelet VEGF Content Within Covid-19

Background: Nitric oxide (NO) regulates both thrombosis and vascular leakage, two of the major complications of severe Covid19. Platelet-derived NO inhibits adhesion/aggregation and within microvascular endothelial cells NO-signalling mediates vascular endothelial growth factor (VEGF/VPF)-induced permeability. Recently, we identified novel platelet subpopulations with a differential ability to produce NO and the presence/absence of endothelial nitric oxide synthase (eNOS). We showed that eNOS-negative (eNOS neg ) platelets initiate adhesion and aggregation, while eNOS-positive (eNOS pos ) platelets limit aggregate growth. As inflammatory cytokines are known to counter-regulate eNOS and VEGF expression, we hypothesized that the ratio of eNOS-negative to -positive platelets may be increased in COVID-19 patients along with their VEGF content. Aims: To determine the eNOS-positive to -negative platelet ratio and platelet VEGF levels within the blood of hospitalized COVID-19 patients. Methods: Platelets were isolated from age- and sex-matched COVID-19 patients (ICU and non-ICU) and COVID-negative healthy controls. Isolated platelets were intracellularly stained for eNOS, VEGF, and for surface CD62P and analyzed using flow cytometry. A multiplex assay was used to measure plasma cytokines. Results: The percentage of eNOS neg platelets within the blood of COVID-19 patients (ICU and non-ICU) was higher than that within healthy controls and their levels correlated with disease severity (81.2±2.8% ICU vs. 66.0 ±3.1% non-ICU vs. 6.1± 1.3% controls, P -value < 0.0001). Accordingly, the percentage of eNOS pos platelets in COVID-19 patients was lower compared to controls, while the platelet VEGF content and surface CD62P of COVID-19 patients in ICU was higher than that of healthy controls. Further, COVID-19 patients demonstrated higher TNFα, IL-6, and IL-1β plasma concentrations than controls. Conclusion: Preliminary data suggests that eNOS-negative to -positive platelet ratios and VEGF content increase with COVID-19 severity, potentially predisposing patients to thrombosis and enhanced vascular permeability upon platelet activation. These platelet changes may be due to the actions of inflammatory cytokines on megakaryocytes.

Lactoferrin Attenuates Intestinal Barrier Dysfunction and Inflammation by Modulating the MAPK Pathway and Gut Microbes in Mice

Deoxynivalenol (DON) is a major mycotoxin present in staple foods (particularly in cereal products) that induces intestinal inflammation and disrupts intestinal integrity. Lactoferrin (LF) is a multifunctional protein that contributes to maintaining intestinal homeostasis and improving host health. However, the protective effects of LF on DON-induced intestinal dysfunction remain unclear. This study aimed to investigate the effects of LF on DON-induced intestinal dysfunction in mice, and its underlying protective mechanism. Male BALB/c mice (5 wk old) with similar body weights were divided into 4 groups (n = 6/group) and treated as follows for 5 wk: Veh [peroral vehicle daily, commercial (C) diet]; LF (peroral 10 mg LF/d, C diet); DON (Veh, C diet containing 12 mg DON/kg); and LF + DON (peroral 10 mg LF/d, DON diet). Intestinal morphology, tight junction proteins, cytokines, and microbial community were determined. Data were analyzed by 2-factor ANOVA or Kruskal-Wallis test. The DON group exhibited lower final body weight (-12%), jejunal villus height (VH; -41%), and jejunal occludin expression (-36%), and higher plasma IL-1β concentration (+85%) and jejunal Il1b mRNA expression (+98%) compared with the Veh group (P < 0.05). In contrast, final body weight (+19%), jejunal VH (+49%), jejunal occludin (+53%), and intelectin 1 protein expression (+159%) were greater in LF + DON compared with DON (P < 0.05). Additionally, jejunal Il1b mRNA expression (-31%) and phosphorylation of p38 and extracellular signal regulated kinase 1/2 (-40% and - 38%) were lower in LF + DON compared with DON (P < 0.05). Furthermore, the relative abundance of Clostridium XIVa (+181%) and colonic butyrate concentration (+53%) were greater in LF + DON compared with DON (P < 0.05). Our study highlights a promising antimycotoxin approach using LF to alleviate DON-induced intestinal dysfunction by modulating the mitogen-activated protein kinase pathway and gut microbial community in mice.

Acute response of biomarkers in plasma from capillary blood after a strenuous endurance exercise bout

PurposeThe present study aims to investigate the acute response of potential exercise-sensitive biomarkers in capillary plasma to an acute incremental running test. In a second step, their concentration was compared to the changes in the venous serum.MethodsThirty-seven active young female and male adults completed a VO2max ramp test on a treadmill. Before and after exercise, capillary blood from the earlobe and venous blood were taken and synchronized. Concentrations of Interleukin- (IL-) 1β, IL-1ra, IL-6, IL-8, IL-17A, Interferon (IFN)-y, CC-chemokine ligand (CCL)-2, Matrix metallopeptidase (MMP)-9, Secreted protein acidic and rich in cysteine (SPARC), Cluster of differentiation (CD)163, S100 Ca2+ -binding protein (S100) A8, S100A9, S100B, Brain-derived neurotrophic factor (BDNF), and Myeloperoxidase (MPO) were determined by magnetic bead-based multiplex assay.ResultsCapillary plasma concentrations of IL-1β, IL-6, IL-8, IL-17A, IFN-y, CCL-2, MMP-9, SPARC, CD163, S100A9, S100B, and BDNF increased after exercise (p < 0.05). Comparing the values from capillary plasma and venous serum, ICCs classified as good were found for IFN-y (post), while the ICCs for IL-1β, IL-8, IL-17A, CCL-2, MMP-9 (post), SPARC, and BDNF (post) were classified as moderate. For all other parameters, only weak ICCs were found.ConclusionAs in the venous serum, there was an increase in most markers in the capillary plasma. However, acceptable to low associations can be found in the concentration levels of these proteins between the compartments. Thus, this source of blood sampling could find some biomarker applications in sports practice.

Risk of non-typhoidal Salmonella vascular infections is increased with degree of atherosclerosis and inflammation: A multicenter study in southern Taiwan.

Atherosclerosis and vascular inflammatory response have been considered as risk factors for non-typhoidal Salmonella (NTS) vascular infection. The study aims to assess the risk of vascular infection by measuring atherosclerosis severity, NTS vascular infection (NTSVI) score, and serum levels of inflammatory markers in people with NTS bacteremia. A prospective observational study was conducted in two medical centers and two regional hospitals. Adults aged ≥50 years with NTS bacteremia who underwent computed tomography (CT) scan for revealing vascular infections were enrolled. The degree of atherosclerosis was scaled by a calcium score determined by a CT scan. Serum concentrations of inflammatory biomarkers were determined in the patients enrolled in a medical center. Fourteen (20.3%) of 69 patients with NTS bacteremia had vascular infections. Calcium scores over the thoracic (12,540 vs. 3,261, P=0.0005) and abdominal (9755 vs. 3,461, P=0.0006) aorta of those with vascular infections were higher than those without vascular infection. All vascular infections were present in the high-risk group (NTSVI score ≥1), yielding a sensitivity of 100% and specificity of 30.9%. Among 17 low-risk patients (NTSVI score <1), none had vascular infections, resulting in a negative predictive value of 100%. Higher plasma concentrations of IL-1β were detected in the cases of vascular infection than those in the control group (23.6 vs. 1.06pg/mL, P=0.001). Atherosclerosis of the aorta which is associated with a positive NTSVI score can predict the occurrence of vascular infections and serum IL-1β could be a biomarker for vascular infection in patients with NTS bacteremia.

Accelerated wound healing and its promoting effects of topical codeine on the healing of full-thickness cutaneous wound, evidences for modulating cytokines involved in pain, inflammation and collagen biosynthesis.

The inflammation and pain occur in all the wounds. Opioids drugs decrease pain and may act as an anti-inflammation. The current study was conducted to investigate the efficiency of the topical uses of Codeine on full-thickness excision wound models by focusing on relationship between pain mediators, inflammation and wound healing rate. Following the induction of anesthesia, a skin wound with a size of 7-mm punch was induced on the dorsal surfaces of each mouse. The mice were divided into five categories: groups I-III were daily administered 2.5%, 5%, and 10% Codeine gel; those in group IV were administered phenytoin cream, and group V (controls) received base ointment. To assess the effects of Codeine gel on the wound healing process, the wound area, histological parameters, and the relative protein expression of CXCR1, CXCR2, IL-6, IL-6R, PDGF, PDGFR, and COL1A along with the plasma concentrations of IL-1β, IL-10, and TNF-α were investigated on days 3, 7, and 14. On days 7 and 14, the wound area was significantly lower in the treated mice compared to the controls (P < 0.05). Angiogenesis, collagen deposition, and epithelium thickness were significantly higher in the treatment groups compared to the control group (P < 0.05). The relative protein expressions of CXCR1, CXCR2, IL-6, and IL-6R and the plasma concentrations of IL-1β and TNF-α were significantly lower in the treated groups. Meanwhile, the relative protein expressions of PDGF, PDGFR, and COL1A and the plasma concentration of IL-10 were significantly higher in the treated mice (P < 0.05). Administration of Codeine gel accelerated wound healing through decreasing the pain mediators, inflammation and promoting proliferative phase.

Association of Interleukin-1 Beta and Interleukin-1 Receptor Antagonist Gene Polymorphisms and Plasma Levels with Diabetic Nephropathy.

Objective We investigated the relationships between interleukin- (IL-) 1β and IL-1 receptor antagonist (IL-1Ra) gene polymorphism and plasma levels in patients with diabetic nephropathy (DN). Methods The genotype and allele frequency distribution of IL-1β and IL-1Ra in 61 patients with DN and 48 healthy controls (HCs) were determined by kompetitive allele-specific PCR (KASP), and the plasma concentrations of IL-1β and IL-1Ra in DN patients and HCs were measured by enzyme-linked immunosorbent assays (ELISA). Results Significant differences were detected in the distribution of IL-1β (−511C/T) genotype and allele frequencies between the DN and HC groups (P < 0.05), with the T genotype being more frequent in DN patients than HCs (OR = 2.84, 95% CI: 1.489–5.416). The IL-1β (+3953C/T) and IL-1Ra (+8006C/T) genotypes and allele frequencies were not significantly different between the two groups (P > 0.05). The plasma IL-1β level was significantly higher (P < 0.01), while the plasma IL-1Ra concentration was significantly lower in the DN group than the HC group (P < 0.05). Furthermore, the plasma IL-1β level was significantly different between IL-1β (−511C/T) locus variants (P < 0.05). Conclusion The IL-1β (−511C/T) gene polymorphism was significantly associated with DN risk in the population of northern Guangxi, China, and the T allele maybe responsible for genetic susceptibility to DN.

A pilot exploration of multi-omics research of gut microbiome in major depressive disorders

The pathophysiology of major depressive disorder (MDD) remains obscure. Recently, the microbiota-gut-brain (MGB) axis’s role in MDD has an increasing attention. However, the specific mechanism of the multi-level effects of gut microbiota on host metabolism, immunity, and brain structure is unclear. Multi-omics approaches based on the analysis of different body fluids and tissues using a variety of analytical platforms have the potential to provide a deeper understanding of MGB axis disorders. Therefore, the data of metagenomics, metabolomic, inflammatory factors, and MRI scanning are collected from the two groups including 24 drug-naïve MDD patients and 26 healthy controls (HCs). Then, the correlation analysis is performed in all omics. The results confirmed that there are many markedly altered differences, such as elevated Actinobacteria abundance, plasma IL-1β concentration, lipid, vitamin, and carbohydrate metabolism disorder, and diminished grey matter volume (GMV) of inferior frontal gyrus (IFG) in the MDD patients. Notably, three kinds of discriminative bacteria, Ruminococcus bromii, Lactococcus chungangensis, and Streptococcus gallolyticus have an extensive correlation with metabolome, immunology, GMV, and clinical symptoms. All three microbiota are closely related to IL-1β and lipids (as an example, phosphoethanolamine (PEA)). Besides, Lactococcus chungangensis is negatively related to the GMV of left IFG. Overall, this study demonstrate that the effects of gut microbiome exert in MDD is multifactorial.

The Potential Role of Proinflammatory Cytokines and Complement Components in the Development of Drug-Induced Neuropathy in Patients with Multiple Myeloma.

The launch of novel chemotherapeutic agents—in particular, proteasome inhibitors and immunomodulatory drugs—dramatically changed multiple myeloma (MM) therapy, improving the response rate and prolonging progression-free survival. However, none of the anti-MM drugs are deprived of side effects. Peripheral neuropathy (PN) seems to be one of the most pressing problems. Despite extensive research in this area, the pathogenesis of drug-induced peripheral neuropathy (DiPN) has not yet been fully elucidated. In the present study, we aimed to assess the potential relationship between proinflammatory factors and the development of PN in MM patients with particular emphasis on the application of VTD (bortezomib, thalidomide, dexamethasone) regimen. Our analysis identified increased concentrations of CCL2, IL-1β, and IFN-γ in plasma of MM patients during treatment, both with and without symptoms of PN, compared with untreated neuropathy-free MM patients. At the same time, the plasma concentration of IL-1β in patients with neuropathy was significantly increased compared with patients without PN before and during treatment. Moreover, the results were enhanced at the transcript level by performing global mRNA expression analysis using microarray technology. The most significant changes were observed in the expression of genes responsible for regulating immunological and apoptotic processes. An in-depth understanding of the mechanisms responsible for the development of DiPN might in the future reduce the incidence of PN and accelerate diagnosis, allowing the choice of neuropathy-free treatment strategies for MM.

Effects of NLRP3 inflammasome blockade on postresuscitation cerebral function in a rat model of cardiopulmonary resuscitation

Cardiac arrest (CA) remains a major public health issue. Inflammatory responses with overproduction of interleukin-1β regulated by NLRP3 inflammasome activation play a crucial role in cerebral ischemia/reperfusion injury. We investigated the effects of the selective NLRP3-inflammasome inhibitor MCC950 on post-resuscitation cerebral function and neurologic outcome in a rat model of cardiac arrest. Thirty-six male rats were randomized into the MCC950 group, the control group, or the sham group (N = 12 of each group). Each group was divided into a 6 h non-survival subgroup (N = 6) and a 24 h survival subgroup (N = 6). Ventricular fibrillation (VF) was electrically induced and untreated for 6 min, followed by 8 min of precordial compressions and mechanical ventilation. Resuscitation was attempted with a 4J defibrillation. Either MCC950 (10 mg/kg) or vehicle was injected intraperitoneally immediately after the return of spontaneous circulation (ROSC). Rats in the sham group underwent the same surgical procedures without VF and CPR. Brain edema, cerebral microcirculation, plasma interleukin Iβ (IL-1β), and neuron-specific enolase (NSE) concentration were measured at 6 h post-ROSC of non-survival subgroups, while 24 h survival rate, neurological deficits were measured at 24 h post-ROSC of survival subgroups. Post-resuscitation brain edema was significantly reduced in animals treated with MCC950 (p < 0.05). Cerebral perfused vessel density (PVD) and microcirculatory flow index (MFI) values were significantly higher in the MCC950 group compared with the control group (p < 0.05). The plasma concentrations of IL-1β and NSE were significantly decreased in animals treated with MCC950 compared with the control group (p < 0.05). 24 h-survival rate and neurological deficits score (NDS) was also significantly improved in the MCC950 group compared with the control group (p < 0.05). NLRP3 inflammasome blockade with MCC950 at ROSC reduces the circulatory level of IL-1β, preserves cerebral microcirculation, mitigates cerebral edema, improves the 24 h-survival rate, and neurological deficits.

The Effect of Intravenous Autologous Activated Platelet-Rich Plasma Therapy on "Profibrotic Cytokine" IL-1β Levels in Severe and Critical COVID-19 Patients: A Preliminary Study.

Introduction Elevated concentration of proinflammatory cytokines followed by hyperinflammation is one of the hallmarks of severe and critical COVID-19. In the short term, this may result in ARDS and lung injury; subsequently, this may cause pulmonary fibrosis—a disease with poor prognosis—in the long run. Among the cytokines, interleukin-1β (IL-1β) is one of the most overexpressed in COVID-19. We speculate that administration of intravenous activated autologous platelet-rich plasma (aaPRP), which contains interleukin-1 receptor antagonist (IL-1RA), would lower IL-1β levels and benefit the severe and critical COVID-19 patients. Methods After acquiring ethical clearance, we recruited 12 adult COVID-19 patients of both sexes from the Koja Regional Hospital (Jakarta, Indonesia) ICU. After selection, seven patients were included and divided into two groups, severe and critical. In addition to three doses of aaPRP, both groups received the same treatment of antiviral, steroid, and antibiotics. Quantification of plasma IL-1β levels was performed by beads multiplex assay a day before the first aaPRP administration and a day after the second and third aaPRP administration. PaO2/FiO2 ratio and lung injury scores were evaluated a day before and a day after each aaPRP administration. Results Severe and critical patients' initial plasma IL-1β concentration was 4.71 pg/mL and 3.095 pg/mL, respectively. After 2 treatments with aaPRP, severe patients' plasma IL-1β concentration decreased 12.48 pg/mL, while critical patients' plasma IL-1β concentration increased to 18.77 pg/mL. Furthermore, after 3 aaPRP treatments, significant amelioration of patients' PaO2/FiO2 ratio from 71.33 mmHg at baseline to 144.97 mmHg was observed (p < 0.05). However, no significant improvement in lung injury score was observed in severe and critical groups. All severe patients and one critical patient recovered. Conclusion The use of aaPRP may prevent pulmonary fibrosis in severe COVID-19 patients through the reduction of patients' plasma IL-1β concentration and the amelioration of PaO2/FiO2 ratio.

A Pilot Exploration of Multi-Omics Research of Gut Microbiome in Major Depressive Disorders

Background: The pathophysiology of major depressive disorder (MDD) remains obscure. Recently, the microbiota-gut-brain (MGB) axis’s role in MDD has an increasing attention. But there are very few studies on the correlations of the gut microbiota with all three omics, including immunology, metabolomics, and brain structure in MDD. Methods: The data of metagenomics, metabolomic, inflammatory factors, and MRI scanning are collected from the two groups including 24 drug-naive MDD patients and 26 healthy controls (HCs). Then, the correlation analysis is performed in all omics. Findings: The results confirmed that there are many markedly altered differences, such as elevated Actinobacteria abundance, plasma IL-1β concentration, lipid, vitamin, and carbohydrate metabolism disorder, and diminished grey matter volume (GMV) of inferior frontal gyrus (IFG) in the MDD patients. Notably, three kinds of discriminative bacteria, Ruminococcus bromii, Lactococcus chungangensis, and Streptococcus gallolyticus have an extensive correlation with metabolome, immunology, GMV, and clinical symptoms. All three microbiota are closely related to IL-1β and lipids (for example, phosphoethanolamine (PEA)). Besides, Lactococcus chungangensis is negatively related to the GMV of left IFG. Interpretation: Overall, this study demonstrate that the effects of gut microbiome exert in MDD is multifactorial. Funding: This work was supported by the National Natural Science Foundation of China (No. 81601182), the grant 2015C03040 of the major subject of Zhejiang Province, and the Natural Science Foundation of Zhejiang Province (LQ20H090010). Declaration of Interest: The authors declare no conflict of interest. Ethical Approval: Ethical approval was obtained from the local Ethics Committee at the First Affiliated Hospital, College of Medicine, Zhejiang University, China.