scholarly journals Early Treatment of Interleukin-33 Can Attenuate Lupus Development in Young NZB/W F1 Mice

Author(s):  
Fatin Nurizzati Mohd Jaya ◽  
Zhongyi Liu ◽  
Godfrey Chi-Fung Chan

Interleukin-33 (IL-33), a member of the IL-1 cytokine family has been recently associated with the development of autoimmune diseases, including SLE. IL-33 is an alarmin and a pleiotropic cytokine that affects various types of immune cells via binding to its receptor, ST2. In this study, we determine the impact of intraperitoneal IL-33 treatments in young lupus, NZB/W F1 mice. Mice were treated from the age of 6 to 11 weeks. We then assessed the proteinuria level, renal damage, survival rate, and anti-dsDNA antibodies. The induction of regulatory B (Breg) cells and changes in gene expression were also examined. In comparison to the control group, young NZB/W F1 mice administered with IL-33 had a better survival rate as well as reduced proteinuria level and lupus nephritis. IL-33 treatments significantly induced IgM anti-dsDNA antibody, IL-10 expressing Breg cells, and alternatively induced M2 macrophage gene signatures. These results imply that IL-33 exhibit regulatory roles during lupus onset via the expansion of protective IgM anti-dsDNA as well as regulatory cells such as Bregs and M2 macrophages.

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2448
Author(s):  
Fatin Nurizzati Mohd Jaya ◽  
Zhongyi Liu ◽  
Godfrey Chi-Fung Chan

Interleukin-33 (IL-33), a member of the IL-1 cytokine family, has been recently associated with the development of autoimmune diseases, including systemic lupus erythematosus (SLE). IL-33 is an alarmin and a pleiotropic cytokine that affects various types of immune cells via binding to its receptor, ST2. In this study, we determine the impact of intraperitoneal IL-33 treatments in young lupus, NZB/W F1 mice. Mice were treated from the age of 6 to 11 weeks. We then assessed the proteinuria level, renal damage, survival rate, and anti-dsDNA antibodies. The induction of regulatory B (Breg) cells, changes in the level of autoantibodies, and gene expression were also examined. In comparison to the control group, young NZB/W F1 mice administered with IL-33 had a better survival rate as well as reduced proteinuria level and lupus nephritis. IL-33 treatments significantly increased the level of IgM anti-dsDNA antibodies, IL-10 expressing Breg cells, and alternatively-induced M2 macrophage gene signatures. These results imply that IL-33 exhibits a regulatory role during lupus onset via the expansion of protective IgM anti-dsDNA as well as regulatory cells such as Breg cells and M2 macrophages.


Author(s):  
Hassan Ghorbani-Choboghlo ◽  
Donya Nikaein ◽  
Ali-Reza Khosravi ◽  
Reza Rahmani ◽  
Zohreh Farahnejad

ABSTRACT     Background and Objectives: Probiotics are live microorganisms that, when administered in an adequate amount, confer a health benefit on the host through the gut. Saccharomyces cerevisiae is a widespread yeast found in nature. This microor- ganism has been used as a probiotic agent in recent years. In this study, the effect of microencapsulation on survival rate of S. cerevisiae var. boulardii in the simulated gastrointestinal tract medium and the impact of microencapsulated S. cerevisiae var. boulardii on some serum biochemical factors in a rat model was evaluated. Materials and Methods: 30 male wistar rats were divided into three groups (control, rats receiving microencapsulated S. cerevisiae var. boulardii, and rats receiving S. cerevisiae var. boulardii alone). The probiotic was gavaged at a dosage of 2 gr/ kg BW for 8 weeks. Blood was collected from rats at the end of the treatment period and biochemical factors were measured using Mancompany kits. Results: The results showed a significant increase in viability of microencapsulated S. cerevisiae var. boulardii in compar- ison with free S. cerevisiae var. boulardii (p<0.05). Weight of rats in probiotic treated groups was significantly higher in comparison with the control group (p<0.05). Moreover, probiotic treatment reduced mean levels of triglycerides, cholesterol, free blood sugar and liver enzymes in rats. Conclusion: Microencapsulation could increase the survival rate of yeast probiotics in the gastrointestinal tract; however, more studies are needed for better understanding of the exact effect of microencapsulation on probiotics’ function.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 984-984
Author(s):  
Krzysztof Giannopoulos ◽  
Wioletta Kaminska ◽  
Anna Dmoszynska

Abstract Abstract 984 Multiple myeloma (MM) is a immunoproliferative disease which is characterized by the uncontrolled proliferation of plasma cells which is accompanied by defects in the immune system. Abnormalities of function and number of T regulatory cells (Treg), dendritic cells (DC) might be responsible for the immunosuppression in MM. DC and Treg are the most important cells in the immune system, able to control peripheral tolerance as well as response to foreign and tumor antigens. The current study aimed to characterize the frequency of Treg, DC as well as subpopulations of T cells bearing regulatory properties like CD4+GITR+, CD4+CD62L+, CD3+TCRγδ+ along with the concentration of IL-10, TGFβ, IL-6 in patients with MM. Subsequently the influence of therapy on those components of immune system was assessed. The study population consisted of 66 newly diagnosed MM patients (females-29, males-37, median age 66.5 years; range 39–81) admitted to the Department of Hematoonocology Medical University of Lublin. The study was approved by the Local Ethics Committee. Immune cells subpopulations were evaluated by the flow cytometry. Myeloid DC (MDC) were identified as blood dendritic cell antigen-1 (BDCA-1) positive and CD19 negative cells. Plasmacytoid DC (PDC) were characterized as blood dendritic cell antigen-1 (BDCA-2) and CD123 positive cells. We also estimated the frequency of Treg (CD4+CD25hiFOXP3+) and other populations of lymphocytes with regulatory function such as: CD4+GITR+, CD4+CD62L+, CD3+TCRγδ+. We used enzyme linked (ELISA) assay to detect cytokines IL-10, IL-6, TGFβ in serum of MM patients. In the current study we observed that the percentage of both MDC and PDC was lower in MM compared to control group (0.16% vs. 0.19% and 0.03% vs. 0.12%, respectively). The frequency of Treg was significantly higher in MM patients compared to healthy control (6.16% vs 0.05%). Also, the percentages of CD4+GITR+, CD4+CD62L+ were increased compared to healthy volunteers (95.19% vs 78% and 10.35% vs 0.42%, respectively). The frequency of CD3+TCRγδ+ was lower compared to control group (2.82% vs 6.05%). We further assessed the influence of certain immune cells frequencies on clinical behavior of MM patients. We found that patients with higher percentages of Treg live shorter (median survival 21 months vs not-reached, p=0.013, Figure 1). Serum levels of cytokines IL-10, IL-6, TGFβ were increased in MM compared to control group (1.16pg/mL vs 0.91pg/mL for IL-10; 3.74pg/mL vs 2.12pg/mL for IL-6; 32233.5pg/mL vs 3877.23pg/mL for TGFβ). During therapy we detected significant lowering concentration of IL-10, to higher extent in responders. In conclusion our results identified several abnormalities of immune system in MM. The dysfunction of immune system (decreased antigen presentation along with increased frequencies of suppressive cells and cytokines) might facilitate progression of the disease and infectious complications. The most important finding of our study is the key function of Treg in modulation of overall survival of MM patients. Overall survival by low (Treg low – below the median) and high (Treg hi – above the median) T regulatory cells frequencies of multiple myeloma patients. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Ito ◽  
S Oshima ◽  
H Ishii ◽  
H Takahashi ◽  
N Umemoto ◽  
...  

Abstract Background Endovascular therapy (EVT) using self-expandable bare nitinol stent (BNS) has been commonly accepted in patients with symptomatic femoropopliteal (FP) occlusive disease. However, poor clinical outcomes in hemodialysis (HD) patients are major problems. We investigated the impact of HD on clinical outcome after EVT in patients with FP disease. Methods A total of 427 consecutive HD patients undergoing successful EVT with BNS for FP disease were enrolled with 157 non-HD patients as a control group. They were followed-up for 5 years. We collected data on target lesion revascularization (TLR) rate, and limb salvage rate as well as survival rate. Propensity-score matching analysis was performed to investigate the true impact of HD on the outcome. Results Critical limb ischemia was observed in 44.0% of overall population (43.0% in HD group vs. 46.8% in non-HD group, p=0.42). Rates of diabetes (67.1% vs. 58.1%, p=0.045) and coronary artery disease (73.5% vs. 58.3%, p=0.0008) were higher, while age (70±10 years old vs. 76±10 years old, p&lt;0.0001) and TASC2 C/D lesion (27.9% vs. 44.6%, p=0.0002) were lower in HD group compared to non-HD group. Pre-procedural C-reactive protein level (0.4mg/l vs. 0.3mg/l, p=0.045) was higher and serum albumin level (3.6g/dl vs. 3.8g/dl, p=0.0045) was lower in HD group than those in non-HD group. The freedom rate from TLR at 5 years was significantly lower in HD group than in non-HD group [47.2% vs. 65.2%, hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.23–2.64, p=0.0017]. The limb salvage rate was comparable between the groups (93.3% vs. 97.1%, HR 1.57, 95% CI 0.58–5.47, p=0.41), while the survival rate was significantly lower in HD group compared to non-HD group (60.6% vs. 86.0%, HR 2.53, 95% CI 1.56–4.36, p=0.0002). After propensity-score analysis, 250 patients (125 in each group) were matched without any difference of clinical characteristics in both groups. In the matched cohort, the freedom rate from TLR was still lower in HD group compared to non-HD group (46.7% vs. 66.6%, HR 2.25, 95% CI 1.35–3.87, p=0.0019). The adjusted limb salvage rate was consistently similar between the groups (95.4% vs. 97.3%, HR 1.10, 95% CI 0.20–5.94, p=0.91). Also, the adjusted survival rate was lower in HD group than in non-HD group (47.6% vs. 89.9%, HR 3.60, 95% CI 1.89–7.44, p&lt;0.0001). Conclusion The freedom rate from TLR at 5 years after BNS implantation for FP disease were significantly lower in HD group than in non-HD group, though the limb salvage rate was similar between the groups. The survival rate was consistently lower in HD group compared to non-HD group. HD status had a great impact on TLR and mortality after EVT with BNS in patients with FP disease. Funding Acknowledgement Type of funding source: None


2000 ◽  
Vol 55 (4) ◽  
pp. 129-136 ◽  
Author(s):  
Cláudio Bresciani ◽  
Joaquim Gama-Rodrigues ◽  
Victor Strassmann ◽  
Dan L. Waitzberg ◽  
Mitsunori Matsuda ◽  
...  

Several drugs and their associations are being used for adjuvant or complementary chemotherapy with the aim of improving results of gastric cancer treatment. The objective of this study was to verify the impact of these drugs on nutrition and on survival rate after radical treatment of 53 patients with gastric cancer in stage III of the TNM classification. A control group including 28 patients who had only undergone radical resection was compared to a group of 25 patients who underwent the same operative technique followed by adjuvant polychemotherapy with FAM (5-fluorouracil, Adriamycin, and mitomycin C). In this latter group, chemotherapy toxicity in relation to hepatic, renal, cardiologic, neurological, hematologic, gastrointestinal, and dermatological functions was also studied. There was no significant difference on admission between both groups in relation to gender, race, macroscopic tumoral type of tumor according to the Borrmann classification, location of the tumor in the stomach, length of the gastric resection, or response to cutaneous tests on delayed sensitivity. Chemotherapy was started on average, 2.3 months following surgical treatment. Clinical and laboratory follow-up of all patients continued for 5 years. The following conclusions were reached: 1) The nutritional status and incidence of gastrointestinal manifestation were similar in both groups; 2) There was no occurrence of cardiac, renal, neurological, or hepatic toxicity or death due to the chemotherapeutic method per se; 3) Dermatological alterations and hematological toxicity occurred exclusively in patients who underwent polychemotherapy; 4) There was no significant difference between the rate and site of tumoral recurrence, the disease-free interval, or the survival rate of both study groups; 5) Therefore, we concluded, after a 5-year follow-up, chemotherapy with the FAM regimen did not increase the survival rate.


2018 ◽  
Vol 2018 ◽  
pp. 1-15
Author(s):  
Yongfang Wang ◽  
Ke Ren ◽  
Lizhi Xie ◽  
Wenge Sun ◽  
Yi Liu ◽  
...  

Purpose. To determine the optimal time interval of repeated intravenous injections of iodixanol in rat model and to identify the injury location and causes of renal damage in vivo. Materials and Methods. Rats were randomly divided into Control group, Group 1 with one iodixanol injection, and Group 2 with two iodixanol injections. Group 2 was subdivided into 3 cohorts according to the interval between the first and second iodixanol injections as 1, 3, and 5 days, respectively. Blood oxygen level-dependent (BOLD) imaging and diffusion weighted imaging (DWI) were performed at 1 hour, 1 day, 3 days, 5 days, and 10 days after the application of solutions. Results. Compared with Group 1 (7.2%), Group 2 produced a remarkable R2⁎ increment at the inner stripe of the renal outer medulla by 15.37% (P=0.012), 14.83% (P=0.046), and 13.53% (P>0.05), respectively, at 1 hour after repeated injection of iodixanol. The severity of BOLD MRI to detect renal hypoxia was consistent with the expression of HIF-1α and R2⁎ was well correlated with HIF-1α expression (r=0.704). The acute tubular injury was associated with urinary NGAL and increased significantly at 1 day. Conclusions. Repetitive injection of iodixanol within a short time window can induce acute kidney injury, the impact of which on renal damage in rats disappears gradually 3–5 days after the injections.


Hand ◽  
2020 ◽  
pp. 155894472093920
Author(s):  
Grace C. Keane ◽  
Deng Pan ◽  
Joseph Roh ◽  
Ellen L. Larson ◽  
Lauren Schellhardt ◽  
...  

Background: Therapeutic electrical stimulation (ES) applied to repaired nerve is a promising treatment option to improve regeneration. However, few studies address the impact of ES following nerve graft reconstruction. The purpose of this study was to determine if ES applied to a nerve repair using nerve isograft in a rodent model could improve nerve regeneration and functional recovery. Methods: Adult rats were randomized to 2 groups: “ES” and “Control.” Rats received a tibial nerve transection that was repaired using a tibial nerve isograft (1.0 cm length), where ES was applied immediately after repair in the applicable group. Nerve was harvested 2 weeks postrepair for immunohistochemical analysis of axon growth and macrophage accumulation. Independently, rats were assessed using walking track and grid-walk analysis for up to 21 weeks. Results: At 2 weeks, more robust axon regeneration and greater macrophage accumulation was observed within the isografts for the ES compared to Control groups. Both walking track and grid-walk analysis revealed that return of functional recovery was accelerated by ES. The ES group demonstrated improved functional recovery over time, as well as improved recovery compared to the Control group at 21 weeks. Conclusions: ES improved early axon regeneration into a nerve isograft and was associated with increased macrophage and beneficial M2 macrophage accumulation within the isograft. ES ultimately improved functional recovery compared to isograft repair alone. This study supports the clinical potential of ES to improve the management of nerve injuries requiring a nerve graft repair.


2016 ◽  
Vol 311 (3) ◽  
pp. F555-F561 ◽  
Author(s):  
Shireen Hashmat ◽  
Nathan Rudemiller ◽  
Hayley Lund ◽  
Justine M. Abais-Battad ◽  
Scott Van Why ◽  
...  

Immune cells in the kidney are implicated in the development of hypertension and renal damage in the Dahl salt-sensitive (SS) rat. Interestingly, interleukin 6 (IL-6) mRNA is 54-fold higher in T-lymphocytes isolated from the kidney compared with circulating T-lymphocytes. The present experiments assessed the role of IL-6 in the development of SS hypertension by treating rats ( n = 13–14/group) with an IL-6 neutralizing antibody or normal IgG during an 11-day period of high-salt (4.0% NaCl chow) intake. The mean arterial pressure (MAP) and urine albumin excretion rates (Ualb) were not different between the groups fed low salt (0.4% NaCl). Following 11 days of drug treatment and high salt, however, the rats receiving anti-IL-6 demonstrated a 47% reduction of IL-6 in the renal medulla compared with control SS. Moreover, the increase in MAP following 11 days of high-NaCl intake was significantly attenuated in SS administered anti-IL-6 compared with the control group (138 ± 3 vs. 149 ± 3 mmHg) as was the salt-induced increase in Ualb and glomerular and tubular damage. To investigate potential mechanisms of action, a flow cytometric analysis of immune cells in the kidney ( n = 8–9/group) demonstrated that the total number of monocytes and macrophages was significantly lower in the treatment vs. the control group. The total number of T- and B-lymphocytes in the kidneys was not different between groups. These studies indicate that IL-6 production may participate in the development of SS hypertension and end-organ damage by mediating increased infiltration or proliferation of macrophages into the kidney.


2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Thorsten Feldkamp ◽  
Anja Bienholz ◽  
Andreas Paul ◽  
Fuat H. Saner

Abstract Background: Patients following liver transplantation are at risk to develop acute kidney injury (AKI). The aim of our study was to assess risk factors for the development of AKI and the impact of AKI on the outcome of patients after liver transplantation (OLT). Patients and methods: In this retrospective study, we analyzed 149 patients undergoing OLT from 1/2004 to 12/2007. AKI was defined according to the KDIGO definition representing the AKIN and the RIFLE classification, and according to the need for renal replacement therapy (RRT). Results: According to the AKIN criteria alone 14 patients, according to the RIFLE criteria alone no patient and according to both definitions 30 patients developed AKI. RRT was required in 54 patients experiencing AKI, whereas 51 patients did not develop AKI. Pre OLT serum creatinine (SCr) significantly predicted the development of AKI requiring RRT, but not AKI without RRT requirement. Survival rate was significantly inferior after 28 days, one or three years in patients with AKI requiring RRT (70.4, 46.4, 44.4% vs. 100, 92.2, 90.2%, P &lt; 0.001). There was no difference in survival between patients experiencing AKI according to the RIFLE or AKIN criteria without RRT requirement and patients without AKI. Conclusion: Pre OLT renal dysfunction assessed by SCr was the most important risk factor predicting severe forms of AKI, but not milder forms of AKI. AKI requiring RRT had a detrimental impact on patients’ survival, whereas milder forms of AKI were not associated with a worse outcome.


2004 ◽  
Vol 10 (1) ◽  
pp. 59-66
Author(s):  
Agoes Soegianto ◽  
Nia Adiani Primarastri ◽  
Dwi Winarni

The purpose of this research was to find out the impact of cadmium on the structure of gills, hepatopancreas and on survival of shrimp. The shrimp was divided into four groups. Group I (control) was exposed to 0 ppb of cadmium, group II exposed to10 ppb of Cd, group III exposed to 20 ppb of Cd and group IV exposed to 30 ppb of Cd. Three replications were applied in each treatment. Survival rate data were collected everyday, and every two days the water was substituted with new water. The experiment was stoped when 50 percent of shrimps dead. The rest of shrimps were prepared for histological study. All data were subjected on Kolmogorov-Smirnov (distribution test) then continued with ANOVA test and Kruscal-Wallis tests. The result of this experiment showed that structural damage on gills and hepatopancreas increase with increasing cadmium concentration in medium. The lamella of shrimp from control group did not show hyperplasia and necrosis; in second group: 24.02 percent of lamella showed hyperplasia, 2.77 percent necrosis and 28.02 percent vacuolization; third group: 70.01 percent of lamella showed hyperplasia, 20.60 percent necrosis and 48.79 percent vacuolization; fourth group: 32.60 percent of lamella demonstrated hyperplasia, 57.35 percent necrosis and 97.50 percent vacuolization. Increasing the structural damage of gills and hepatopancreas, it cause the decrease on survival rate of shrimp.


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