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Objective To investigate the effect of BIS-guided closed-loop target-controlled infusion on perioperative Th1/Th2 balance in elderly patients undergoing laparoscopic radical gastrectomy under different anesthesia and sedation depths. Methods We applied random number table method to divide 73 elderly patients undergoing elective laparoscopic radical gastrectomy into BIS closed-loop target-controlled infusion group with BIS value of 55(group H, n=36) and BIS value of 45(group L, n=37).Intravenous blood samples were collected immediately before surgery (T1), 2h after surgery (T2), 24h after surgery (T3) and 72h after surgery (T4).IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ were determined by flow cytometry microsphere array.We compared operation duration, postoperative PACU stay time and postoperative hospitalization time between two groups. Results Compared with T1, IL-6 and IL-10 concentration in group H at T2, T3 and T4 significantly increased (P < 0.05), IL-4 and TNF-α in group H at T4 were significantly increased (P < 0.05), IL-2 and IFN-γ in group H at T2 and T4 were significantly increased (P < 0.05), the concentration of IL-6 and IL-10 in group L at T2, T3 and T4 were increased (P < 0.05), IL-2 in group L at T4 was decreased (P < 0.05), and IFN-γ/IL-6 in two groups were decreased at T2, T3 and T4(P < 0.05).Compared with group L, IL-6 and IL-10 in group H were significantly increased at T2(P < 0.05), IFN-γ/IL-6 in group H was significantly decreased (P < 0.05), IL-2 and IL-10 in group H were significantly increased at T4(P < 0.05).Operation duration, postoperative PACU stay time and postoperative hospitalization time had no statistical significance between two groups (P > 0.05). Conclusion The anesthesia and sedation depth of BIS-guided closed-loop target-controlled infusion set at 45 is better than 55 in maintaining Th1/Th2 balance in elderly patients undergoing laparoscopic radical gastrectomy, but it has no obvious effect on long-term prognosis.
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ObjectiveTo explore the anti-abortional effect of Pangshi Antai Zhixue decoction and its mechanism in helper T lymphocyte 1 （Th1）/Th2 balance in the decidual tissues of spontaneous abortion rats with heat syndrome， based on the p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. MethodAconiti Lateralis Radix Praeparata， Zingiberis Rhizoma， and Cinnamomi Cortex decoction was used to replicate the rat model of spontaneous abortion with heat syndrome. The spontaneous abortion rats with heat syndrome were randomly divided into model group， aspirin group （5.25 mg·kg-1）， dydrogesterone group （3.02 mg·kg-1）， Pangshi Antai Zhixue decoction high-dose （44 g·kg-1）， medium-dose （22 g·kg-1）， and low-dose （11 g·kg-1） groups， with ten rats in each group. Ten normal rats were divided into a normal group. Rats in each group were given corresponding drugs， Once a day for 12 d. After 24 h of the last administration， blood was collected from the abdominal aorta. The enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of β-human chorionic gonadotropin （β-HCG）， progesterone （P）， estradiol （E2）， γ interferon （IFN-γ）， and interleukin-4 （IL-4） in rat serum. The uterus and meconium tissues of rats were collected to determine the number and rate of miscarriages. Western blot was used to detect GATA3， T-bet， p38 MAPK， and its phosphorylation in the decidual tissue. ResultAs compared with the normal group， the number of live births， the β-HCG， P， E2， and IL-4 in the serum， and the GATA3 protein expression in the decidual tissue in the model group were reduced （P<0.01）， whereas the number and rate of miscarriages， IFN-γ in the serum， and the expression of p-p38 MAPK and T-bet protein levels in the demolded tissues increased （P<0.01）. As compared with the model group， the number of live births， the β-HCG， P， E2， and IL-4 in the serum， and the GATA3 protein expression in the decidual tissue in the Pangshi Antai Zhixue decoction medium-dose group increased （P<0.01）， whereas the number and rate of miscarriages， IFN-γ in the serum， and the expression of p-p38 and T-bet protein levels in the demolded tissues reduced （P<0.01）. As compared with the aspirin group， the P， E2， and IL-4 in the serum of rats in the dydrogesterone group and the Pangshi Antai Zhixue decoction high-dose and medium-dose groups increased （P<0.01）， the number of live births in the Pangshi Antai Zhixue decoction medium-dose group increased （P<0.01）， and the β-HCG and IFN-γ in the serum of rats in the dydrogesterone group decreased （P<0.01）. The number and rate of miscarriages， IFN-γ in the serum， and T-bet and GATA3 levels in the decidual tissues of rats in the Pangshi Antai Zhixue decoction medium-dose group decreased （P<0.05）. Compared with the Pangshi Antai Zhixue decoction medium-dose group， the low-dose group， high-dose group， and dydrogesterone group showed increased number and rate of miscarriages （P<0.05）， and the high-dose group and dydrogesterone group decreased the number of live birth （P<0.01）. The IFN-γ in the serum and p-p38 MAPK and T-bet protein in the decidual tissue in the low-dose group， and the p-p38 MAPK and T-bet protein in the decidual tissue in the high-dose group all increased （P<0.05）. The β-HCG， P， and E2 in the serum of rats in the Pangshi Antai Zhixue decoction low-dose group， dydrogesterone group， and aspirin group decreased （P<0.01）， and the IL-4 in the serum and GATA3 in the decidual tissue of rats in the Pangshi Antai Zhixue decoction low-dose and high-dose group and the dydrogesterone group decreased （P<0.01）. ConclusionPangshi Antai Zhixue decoction realizes the effect of fetal protection by regulating the activation of p38 MAPK signal pathways and Th1/Th2 balance.
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ObjectiveTo explore the anti-abortional effect of Pangshi Antai Zhixue decoction and its mechanism in helper T lymphocyte 1 （Th1）/Th2 balance in the decidual tissues of spontaneous abortion rats with heat syndrome， based on the p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. MethodAconiti Lateralis Radix Praeparata， Zingiberis Rhizoma， and Cinnamomi Cortex decoction was used to replicate the rat model of spontaneous abortion with heat syndrome. The spontaneous abortion rats with heat syndrome were randomly divided into model group， aspirin group （5.25 mg·kg-1）， dydrogesterone group （3.02 mg·kg-1）， Pangshi Antai Zhixue decoction high-dose （44 g·kg-1）， medium-dose （22 g·kg-1）， and low-dose （11 g·kg-1） groups， with ten rats in each group. Ten normal rats were divided into a normal group. Rats in each group were given corresponding drugs， Once a day for 12 d. After 24 h of the last administration， blood was collected from the abdominal aorta. The enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of β-human chorionic gonadotropin （β-HCG）， progesterone （P）， estradiol （E2）， γ interferon （IFN-γ）， and interleukin-4 （IL-4） in rat serum. The uterus and meconium tissues of rats were collected to determine the number and rate of miscarriages. Western blot was used to detect GATA3， T-bet， p38 MAPK， and its phosphorylation in the decidual tissue. ResultAs compared with the normal group， the number of live births， the β-HCG， P， E2， and IL-4 in the serum， and the GATA3 protein expression in the decidual tissue in the model group were reduced （P<0.01）， whereas the number and rate of miscarriages， IFN-γ in the serum， and the expression of p-p38 MAPK and T-bet protein levels in the demolded tissues increased （P<0.01）. As compared with the model group， the number of live births， the β-HCG， P， E2， and IL-4 in the serum， and the GATA3 protein expression in the decidual tissue in the Pangshi Antai Zhixue decoction medium-dose group increased （P<0.01）， whereas the number and rate of miscarriages， IFN-γ in the serum， and the expression of p-p38 and T-bet protein levels in the demolded tissues reduced （P<0.01）. As compared with the aspirin group， the P， E2， and IL-4 in the serum of rats in the dydrogesterone group and the Pangshi Antai Zhixue decoction high-dose and medium-dose groups increased （P<0.01）， the number of live births in the Pangshi Antai Zhixue decoction medium-dose group increased （P<0.01）， and the β-HCG and IFN-γ in the serum of rats in the dydrogesterone group decreased （P<0.01）. The number and rate of miscarriages， IFN-γ in the serum， and T-bet and GATA3 levels in the decidual tissues of rats in the Pangshi Antai Zhixue decoction medium-dose group decreased （P<0.05）. Compared with the Pangshi Antai Zhixue decoction medium-dose group， the low-dose group， high-dose group， and dydrogesterone group showed increased number and rate of miscarriages （P<0.05）， and the high-dose group and dydrogesterone group decreased the number of live birth （P<0.01）. The IFN-γ in the serum and p-p38 MAPK and T-bet protein in the decidual tissue in the low-dose group， and the p-p38 MAPK and T-bet protein in the decidual tissue in the high-dose group all increased （P<0.05）. The β-HCG， P， and E2 in the serum of rats in the Pangshi Antai Zhixue decoction low-dose group， dydrogesterone group， and aspirin group decreased （P<0.01）， and the IL-4 in the serum and GATA3 in the decidual tissue of rats in the Pangshi Antai Zhixue decoction low-dose and high-dose group and the dydrogesterone group decreased （P<0.01）. ConclusionPangshi Antai Zhixue decoction realizes the effect of fetal protection by regulating the activation of p38 MAPK signal pathways and Th1/Th2 balance.
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OBJECTIVES@#To study the expression levels of microRNA-138 (miR-138) and Runt-related transcription factor 3 (RUNX3) in peripheral blood of children with cough variant asthma (CVA) and their regulatory effects on Th1/Th2 balance.@*METHODS@#Sixty-five children with CVA (CVA group) and 30 healthy children (control group) were enrolled. Peripheral venous blood samples were collected for both groups, and CD4@*RESULTS@#Compared with the control group, the CVA group showed significantly decreased levels of IFN-γ and IL-2 from CD4@*CONCLUSIONS@#MiR-138 regulates Th1/Th2 balance by targeting RUNX3 in children with CVA, providing a new direction for the treatment of CVA.
Subject(s)
Child , Humans , Asthma , Core Binding Factor Alpha 3 Subunit/genetics , Cough , Interleukin-13 , MicroRNAs/genetics , Th1 Cells , Th1-Th2 Balance , Th2 CellsABSTRACT
The ongoing outbreak of novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an unprecedented global health crisis. Development of a cure for this devastating disease is currently at full speed, with several vaccines against COVID-19 already authorized and administered. Currently, demand for these vaccines far exceeds supply. As such, boosting immunity represents a viable route to halt the rapid spread of SARS-CoV-2 and limit fatalities until vaccines become more readily and widely available. The use of phytochemicals appears to be a promising panacea. Sesamin, a lignan isolated from Sesamum indicum seeds, is known for its potent pharmacological properties, and is therefore hypothesized as a potential candidate in the therapeutic regimen against COVID-19. Herein, we highlight the confirmed therapeutic anti-inflammatory and immune-modulatory potential of sesamin against myriads of respiratory disorders, and tentatively suggest that sesamin may exert similar potent effects against COVID-19. Precisely, we speculate that sesamin may help alleviate COVID-19 via restoring Th1/Th2 balance and preventing inflammation and cytokine storm development. Additionally, we further support the promising role of sesamin against COVID-19 by underscoring the direct evidence, which suggests that sesamin may demonstrate promising inhibitory potential against three important SARS-CoV-2 targets, namely main protease, spike protein, and angiotensin-converting enzyme 2 receptor. Although preliminary, there is ample evidence to propose sesamin as a potential phytotherapeutic and prophylactic candidate against COVID-19. Further in vitro, in vivo, and preclinical studies are required to further substantiate the role of sesamin in the prevention and/or treatment of COVID-19.
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T-helper subtype imbalance is intricate in type 1 diabetes (T1D) and asthma initiation. The role of quercetin in immunedysregulation in comorbid conditions of T1D and asthma is not available. In this study, it was thought worthy toevaluate the role of quercetin on modulating Th1/Th2 cytokine dysregulation in comorbid diabetic asthma. Male Balb/cmice were injected intravenously with alloxan (80 mg/kg) to persuade T1D. Succeeding diabetes introduction, twointraperitoneal sensitizing doses of ovalbumin emulsion (50 µg ovalbumin blended with 2.5 mg alum/sensitization) weregiven on days 3 and 8. Mice were given intranasal challenges of ovalbumin (100 µg ovalbumin/25 µl of sterile saline) ondays 13–15. Oral quercetin treatment (10–30 mg/kg) was given daily on days 3–15. Nasal hyperresponsiveness (NHR)was recorded immediately after Ova challenge on day 16. Bronchoalveolar lavage fluid (BALF), blood, and lungs werecollected 1-hour post NHR for further analysis. Quercetin treatment significantly decreased eosinophils, interleukin-4while increasing interferon-gamma in blood, and BALF and reduced the allergic airway inflammation by inhibitinginflammatory cell infiltration and mucous cell metaplasia. Furthermore, quercetin with a dose of 30 mg/kg demonstrateda significant glucose reduction. Thus, quercetin exerted dose-dependent anti-asthma activity by modulating Th1/Th2balance with glucose-lowering potential in comorbid mice.
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Introduction: The cell-mediated immune response plays an important role in the control of HPV-induced cancers. Cytokines play an important function in host defense against HPV infection by modulating viral infection and polarizing the immune response towards Th1 or Th2 cells. Objective: To evaluate the specific immune response to HPV in vitro in men with and without lesions caused by HPV. Methods: We recruited 31 patients and 11 volunteers and divided them into the following four groups: 12 patients in Group A (HIV+/HPV+); 9 patients in Group B (HIV-/HPV+); 10 patients in Group C (HIV+/ HPV-); and 11 healthy subjects in Group D (HIV-/HPV-). PBMCs culture assays were performed to measure the levels of Th1/Th2/Th17 cytokines (IFN-γ, IL-2, TNF-α, IL-4, IL-10 and IL-17) in cells from patients stimulated with a quadrivalent HPV vaccine (HPV 6, 11, 16 and 18) and the E7 protein of HPV16. Results: The coinfected group A (HIV+/HPV+) showed higher levels of cytokines, especially Th2 cytokines, compared with the other study groups. The coinfected group had significantly higher levels of IL-6 and IL-10, which are Th2 cytokines, compared to the control group (HIV-/HPV-) (p<0.0001 and p<0.0001, respectively). Conclusion: This study reports a high production of cytokines in the coinfected group, suggesting strong immunomodulatory effects by HIV/HPV coinfection. However, further studies should be conducted to confirm these data. Because this group had high levels of Th2 cytokines, especially IL-6 and IL-10, these data suggest that these two cytokines may serve as biomarkers for viral persistence because HIV seropositive patients have a higher HPV persistence and may allow for the progression to more serious injuries to be monitored.
Introdução: A resposta imune celular exerce um importante papel no controle dos cânceres induzidos pela infecção por HPV. As citocinas desempenham um papel importante na defesa do hospedeiro contra a infecção pelo HPV pela modulação da infecção viral e a polarização da resposta imune para células Th1 ou Th2. Objetivo: Avaliar a resposta imune específica in vitro ao HPV em homens com e sem lesões causadas pelo HPV. Métodos: Foram recrutados 31 pacientes e 11 voluntários, divididos em quatro grupos: 12 pacientes no grupo A (HIV+/HPV+); 9 pacientes no grupo B (HIV-/HPV+); 10 pacientes no Grupo C (HIV+/HIV-); e 11 sujeitos saudáveis no grupo D (HIV-/HPV-). Uma cultura de PBMCs foi realizada para medir os níveis de citocinas Th1/ Th2/Th17 (IFN-γ, IL-2, TNF-α, IL-4, IL-10 e IL-17) de células de pacientes estimulados com a vacina quadrivalente para HPV (HPV 6, 11, 16 e 18) e a proteína E7 de HPV-16. Resultados: O grupo A coinfectado (HIV+/HIV+) apresentou altos níveis de citocinas, especialmente citocinas do perfil Th2, comparados com os demais grupos estudados. O grupo coinfectado apresentou níveis significativamente mais elevados de IL-6 e IL-10, citocinas do perfil Th2, comparados ao grupo controle (HIV-/HPV-) (p<0,0001 e p<0,0001, respectivamente). Conclusão: Este estudo reportou uma elevada produção de citocinas no grupo de coinfectados, sugerindo um forte efeito imunomodulatório pela coinfecção HIV/HPV. Entretanto, outros estudos devem ser conduzidos para confirmar estes dados. Devido este grupo apresentar altos níveis de citocinas Th2, especialmente IL-6 e IL-10, esses dados sugerem que essas duas citocinas podem servir como biomarcadores para a persistência viral, uma vez que pacientes soropositivos para HIV apresentam níveis mais altos de persistência pelo HPV e podem permitir que a progressão para lesões mais graves possa ser monitorada.
Subject(s)
Humans , Papillomaviridae , Cytokines , Neoplasms , Immunity , Infections , MenABSTRACT
OBJECTIVE To invest igate the therapeutic effect and mechanism of PPAR gamma agonist on allergic rhinitis(AR) in mice. METHODS AR murine model was established by OVA sensitization and challenge. The behavior observation was used to understand the improvement effect of PIO on AR symptoms. The morphological characteristics of nasal tissues were observed by HE staining. The total RNA was extracted to investigate the level of mRNA expression of Foxp3, T-bet and GATA-3. The changes of CD4+Foxp3+T cells in spleen of mice were analyzed by flow cytometry. RESULTS BALB/c mice received OVA sensitization followed by OVA intranasal challenge, the frequencies of sneezing and nose-scratching increased signif icantly in AR group compared with control group. The frequencies decreased significantly in PIO group, compared with AR group. The continuity of nasal mucosa ciliated columnar epithelium in AR group was destroyed and appeared to be repaired in PIO group. Inflammatory cells infiltration was also markedly decreased by PIO treatment. PIO significantly increased the expression of Foxp3 mRNA(P ＜0.001) compared with AR and control group. There was no significant difference in T-bet between PIO group and AR group, but the expression of GATA-3 mRA in PIO group was significantly lower than AR group. The proportion of CD4+Foxp3+T cells in AR group (4.43％±0.25％) decreased compared with control group (5.19％±0.39％) (P ＜0.001). PIO treatment induced production of Tregs (6.35％±0.37％) compaered with control group(P ＜0.001). CONCLUSION PPAR-gamma agonist can effectively alleviate allergic symptoms of mice and regulate the balance of Th1/Th2. The role of PPAR gamma agonist in the treatment of AR may be the amplification of Tregs by promoting Foxp3 expression.
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Preeclampsia is one of the main causes of high morbidity and mortality of pregnant women and perinatal infants worldwide. Affected by many factors, preeclampsia has a complex pathogen-esis and can cause involvement of multiple organs and systems. Its pathogenesis is still unclear. Current research suggests that maternal immune system indirectly involved in the pathophysiology of preeclampsia change, that is, abnormal activation of innate immune cells and unbalanced differentiation of T helper cell subsets interfere with normal immune regulation, and interact with inflammatory response of the body, which produces cytotoxic environment at the maternal-fetal interface and affects trophoblast inva-sion. Therefore, clarifying the role of the immune system can not only clarify the pathogenesis of pre-eclampsia, but also contribute to the development of diagnosis and treatment of preeclampsia. This paper reviews the research status of immune system in preeclampsia, including innate immunity and adaptive immunity . The immune mechanism of preeclampsia is elaborated mainly from immune regulation mediated by T lymphocyte, natural killer ( NK) cell, macrophage and human leukocyte antigen.
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Objective To investigated the protective effect and immunology mechanism of Astragaloside Ⅳ(Ast) on rat renal ischemia-reperfusion injury model. Methods The SD rats were randomly divided into four group as the control, sham-operation, renal ischemia-reperfusion injury, and Ast treatment groups. Rat serum and urine were collected and detective for kidney function and interleukin cytokines. The kidney tissue was collected for histology exam. The rats in astragaloside group were intraperitoneally injected with 100 mg/kg astragaloside, and the other three groups were intraperitoneally injected with an equal volume of normal saline. The models of renal ischemia-reperfusion injury were prepared to generate in model and astragaloside groups, after 30 minutes of astragaloside injection. The rats with renal ischemia-reperfusion injury model were sacrificed after 24 hours, and the level of blood-urine creatinine, neutrophil gelatinase-associated lipocalin and Kidney damage molecule-1 were determined. The level of Th1 type cytokines (TNF-α, IFN-γ, IL-2) and Th2 type cytokines (IL-4, IL-5, IL-10) in serum were measured by using ELISA. The protein and gene expression of TNF-α, IFN-γ, IL-2, IL-4, IL-5, IL-10 in renal tissue were tested by western blot and PCR, respectively. The pathological changes and apoptosis of renal tissue in each group were detected by HE staining and TUNEL staining, respectively. The expression of CD20 protein in renal tissue was determined by immunohistochemistry. Results Compared with the model group, Ast treatment reduced serum creatinine (58.74 ± 9.44 μmol/L vs. 85.03 ± 23.48 μmol/L), increased creatinine clearance rate (0.81 ± 0.13 ml/min vs. 0.37 ± 0.08 ml/min), and reduce urine neutrophil gelatinase-associated lipocalin (NGAL) (579.34 ± 11.70 pg/ml vs. 827.60 ± 14.48 pg/ml), kidney injury molecule-1 (KIM-1) (105.06 ± 2.10 pg/ml vs. 151.67 ± 3.06 pg/ml) (P<0.05). Compared with the model group, Ast treatment alleviated renal tubular epithelial cell injury and significantly decreased the apoptosis (14.36 ± 1.36% vs. 28.63 ± 2.03%) (P<0.05), and significantly decreased the serum TNF-α (361.44 ± 9.66 pg/ml vs. 515.93 ± 10.61 pg/ml), IFN-γ (64.11 ± 1.21 pg/ml vs. 93.51 ± 2.15 pg/ml), IL-2 (388.33 ± 1.21 pg/ml vs. 557.82 ± 15.29 pg/ml), IL-4 (60.89 ± 1.21 pg/ml vs. 95.56 ± 2.75 pg/ml), IL-5 (94.02 ± 2.81 pg/ml vs. 147.07 ± 3.50 pg/ml), and IL-10 (52.62 ± 2.51 pg/ml vs. 78.22 ± 3.24 pg/ml) (P<0.01). Compared with the model group, Ast treatment significantly decreased the kidney TNF-α mRNA (1.89 ± 0.59 vs. 2.87 ± 0.97), IFN-γ mRNA (3.11 ± 1.02 vs. 5.98 ± 1.52), IL-2 mRNA (1.68 ± 0.44 vs. 4.09 ± 1.65), IL-4 mRNA (2.41 ± 0.81 vs. 4.69 ± 1.62), IL-5 mRNA (1.56 ± 0.19 vs. 2.92 ± 0.55), IL-10 mRNA (1.45 ± 0.14 vs. 2.85 ± 0.32) (P<0.01). The ratio of IL-4 to IFN-γ was basically restored to the level of sham operation group (1.05 ± 0.02 vs. 1.02 ± 0.06) (P<0.01), and CD20 cells in renal tissue was reduced. Conclusions The Th1 and B lymphocytes play an important role in renal ischemia reperfusion injury, and Th2 cells play a protective role. Astragaloside can regulate the imbalance of Th1/Th2 in the early stage after acute renal injury, and alleviate renal tubular injury.
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Objective To investigate the effect of Yiqi-Tuomin decoction combined with triamcinolone acetonide nasal spray on Th1/Th2 balance in allergic rhinitis (AR) and to observe the clinical efficacy.Methods A total of 100 patients who met the inclusion criteria were divided into two groups by random number table method,50 in each group.The control group was treated with triamcinolone acetonide nasal spray.The observation group was given Yiqi-Tuomin decoction on the basis of the control group.Both groups were treated for 4 weeks and followed up for 3 months.Clinical symptom score was performed before and after treatment.The serum level of interferon-γ (IFN-γ) and IL-4 was detected by ELISA,and the ratio of IFN-γ/IL-4 was calculated.The adverse reaction and recurrence rate during treatment was observed and recorded,and the clinical efficacy was evaluated.Results The total effective rate was 94.0％ (47/50) in the observation group and 80.0％ (40/50) in the control group.There was significant difference between the two groups (x2=4.332,P=0.037).After treatment,the serum IFN-γ (95.15 ± 18.49 ng/L vs.83.85 ± 16.20 ng/L,t=3.250) and the ratio of IFN-γ/IL-4 (1.35 ± 0.21 vs.0.93 ± 0.19,t=5.878) significantly increased (P＜0.01),while serum level of IL-4 (71.14 ± 14.15 ng/L vs.89.8 6 ± 17.52 ng/L,t=10.487) significantly decreased in the observation group (P＜0.01).After treatment,the score of nasal obstruction,rhinocnesmus,sneezing and nasal discharge in the observation group were significantly lower than those in the control group (t=11.229,8.921,8.253,10.464,respectively,all Ps＜0.01).Conclusions The Yiqi-Tuomin decoction combined with triamcinolone acetonide nasal spray can significantly improve the clinical symptoms of AR patients,correct the imbalance of Th1/Th2 ratio and improve the immunity of the body.
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OBJECTIVE: To observe the influence of fire needle stimulation at Sihua acupoints combined with chemotherapy on Th1/Th2 imbalance and performance status in the patients with advanced non-small cell lung cancer (NSCLC) so as to investigate its immunological mechanism underlying the improvement of lung cancer. METHODS: Sixty eligible NSCLC inpatients were randomly assigned to a control group and a treatment group (n＝30 cases in each one). The control group was treated with paclitaxel combined with cisplatin (TP) or gemcitabine plus cisplatin (GP) of chemotherapy, and the treatment group was treated with fire needle stimulation at Sihua acupoints (i.e. bilateral Geshu [BL17] and Danshu [BL19]) and with chemotherapy simultaneously. The fire needle stimulation was given once daily for successive 7 days. One day before and 14 days after chemotherapy, the patients' blood samples were collected for assaying the concentrations of Th1 related cytokines (IL-2, IFN-γ) and Th2 related cytokines (IL-4, IL-10) with ELISA. The Karnofsky performance status (KPS) score was used to assess the patient's physical conditions before and 14 days after chemotherapy. RESULTS: Compared with the results before treatment, the levels of IL-2 and IFN-γ concentration increased obviously and the levels of IL-4 and IL-10 concentration as well as KPS score decreased significantly in the treatment group and the control group after treatment (all P<0.01). After treatment, compared with the control group, the levels of IL-2 and IFN-γ concentration in the treatment group increased and the levels of IL-4 and IL-10 concentration decreased (P<0.01); and the decrease amplitude of KPS score in the treatment group was less than that in the control group (P<0.01). CONCLUSION: Fire needle stimulation at Sihua acupoints improves the function of Th1 cells, and reduces the function of Th2 cells. As a result, the balance between Th1 and Th2 has been modified and the deterioration degree of the performance status been alleviated in the patients after chemotherapy.
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Objective To investigate the role of TIGIT signal in Th1/Th2 balance in the process of Schistosoma japonicum in-fection.Methods Male C57BL/6 mice were infected with cercariae of S.japonicum,and normal uninfected mice served as the controls.The percentages of TIGIT+cells,Ki67+CD3+CD4+TIGIT+cells,Ki67+CD3+CD4+TIGIT-cells,IFN-γ+CD3+CD4+TIGIT+cells,IFN-γ+CD3+CD4+TIGIT- cells,IL-4+CD3+CD4+TIGIT+cells and IL-4+CD3+CD4+TIGIT- cells were evaluated in mouse spleen by flow cytometry.Results The proportion of TIGIT+CD4+T cells was higher in the spleen of S.japonicum-infected mice than in the normal uninfected mice(29.30%±0.70% vs.3.09%±0.50%;t=8.834,P<0.01).However,no significant differ-ence in the percentages of TIGIT+CD8+T cells between the infection group and normal controls(3.61% ± 0.26% vs. 3.58% ± 0.16%;t=0.108,P>0.05),and no significant difference was detected in the percentages of TIGIT+cells in non-T cells be-tween the infection group and controls(1.86%±0.19% vs.1.37%±0.17%;t=1.931,P>0.05).In addition,the proportion of Ki67 in the TIGIT+cells was higher than that in the TIGIT-cells(17.03%±0.64% vs.6.59%±0.37%;t=14.09,P<0.01).The Th2/Th1 ratio was higher in the TIGIT+CD4+T cells than in the TIGIT-CD4+T cells(39.28%±3.75% vs.11.79%±1.64%;t=6.721,P<0.01).Conclusion The TIGIT signaling may be involved in the development of Th2 responses in the mice infected with S.japonicum.
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OBJECTIVE@#To observe preventive and therapeutic effects and the mechanism of actions on Zishen Yutai pill combined with progesterone on threatened abortion in rats.@*METHODS@#After pregnancy, 50 SPF female SD rats were selected and divided into control group, model group, progesterone group, Zishen Yutai pill group, and progesterone plus Zishen Yutai pill group (combination group), with 10 rats in each group. The rats of control group and abortion model group were lavaged with 2 mL/kg normal saline on pregnancy day 1 for continuous 10 days. Rats in Zishen Yutai pill group were given 1.575 g/kg/d of Zishen Yutai pill for intragastric administration for continuous 10 days. Rats in progesterone group were given intramuscular injection treatment of 0.1 mL/d progestin, continuous for 10 days. Rats in combination group were given injection therapy of aqueous solution of Zishen Yutai pill for continuous 10 days, and other treatments were the same as previous two groups. Abortion model were established then and live births, numbers of abortion and average rate of abortion were compared between the five groups. Peripheral blood was collected to detect the estradiol (E2) and progestational hormone (P), and obtain ratio of Th1/Th2 cytokines (IL-2, INF-γ, IL-4, IL-10).@*RESULTS@#Significant more live births of rats were found in the control group compared with other four groups (P 0.05) but these levels in the control group and Zishen Yutai pill group were significant lower than that of progesterone group and joint group (P < 0.05). The maternal-fetal interface IL - 4/IL - 2, IL - 10/IL - 2 of model group were balanced deviating to Th1, while the IL-4/IL-2, IL-10/IL-2 of progesterone group, Zishen Yutai pill group and joint group were balanced deviating to Th2, and joint group' deviation was better than progesterone group and Zishen Yutai pill group (P < 0.05).@*CONCLUSIONS@#Zishen Yutai pill combined with progesterone has a significant control effect for threatened abortion, which can obviously increase contents of maternal serums E2 and P, and regulate the Th1/Th2 balance with a remarkable effect.
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Objective To observe preventive and therapeutic effects and the mechanism of actions on Zishen Yutai pill combined with progesterone on threatened abortion in rats. Methods After pregnancy, 50 SPF female SD rats were selected and divided into control group, model group, progesterone group, Zishen Yutai pill group, and progesterone plus Zishen Yutai pill group (combination group), with 10 rats in each group. The rats of control group and abortion model group were lavaged with 2 mL/kg normal saline on pregnancy day 1 for continuous 10 days. Rats in Zishen Yutai pill group were given 1.575 g/kg/d of Zishen Yutai pill for intragastric administration for continuous 10 days. Rats in progesterone group were given intramuscular injection treatment of 0.1 mL/d progestin, continuous for 10 days. Rats in combination group were given injection therapy of aqueous solution of Zishen Yutai pill for continuous 10 days, and other treatments were the same as previous two groups. Abortion model were established then and live births, numbers of abortion and average rate of abortion were compared between the five groups. Peripheral blood was collected to detect the estradiol (E2) and progestational hormone (P), and obtain ratio of Th1/Th2 cytokines (IL-2, INF-γ, IL-4, IL-10). Results Significant more live births of rats were found in the control group compared with other four groups (P 0.05) but these levels in the control group and Zishen Yutai pill group were significant lower than that of progesterone group and joint group (P < 0.05). The maternal–fetal interface IL – 4/IL – 2, IL – 10/IL – 2 of model group were balanced deviating to Th1, while the IL-4/IL-2, IL-10/IL-2 of progesterone group, Zishen Yutai pill group and joint group were balanced deviating to Th2, and joint group’ deviation was better than progesterone group and Zishen Yutai pill group (P < 0.05). Conclusions Zishen Yutai pill combined with progesterone has a significant control effect for threatened abortion, which can obviously increase contents of maternal serums E2 and P, and regulate the Th1/Th2 balance with a remarkable effect.
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BACKGROUND:HLA-DRB1 is related to the pathogenesis of alergic rhinitis. Construction ofHLA-DRB1 gene knockout animal models not only elucidates the pathogenesis of alergic rhinitis, but also provides a good way for the elucidation of the pathogenesis of alergic rhinitis-related diseases. OBJECTIVE:To establish the HLA-DRB1gene knockout animal models. METHODS:Homozygous, wild-type and heterozygous mice were obtained by inbreeding of the heterozygous mice. Confirmed by gene and protein identification, 24 female wild-type (H2-eb1+/+) mice and 12 H2-eb1-/-mice aged 8 weeks were selected according to the random number table. 12 H2-eb1+/+ mice and 12 H2-eb1-/- mice were sensitized with ovalbumin to establish the mouse models of alergic rhinitis. Another 12 mice were sensitized with PBS as comparison. RESULTS AND CONCLUSION:Compared with the control mice, serum levels of ovalbumin-specific IgE and interleukin-4 were significantly increased, while serum level ofγ-interferon was significantly decreased in the mouse models of alergic rhinitis. Serum levels of IgE and interleukin-4 were lower, while serumγ- interferon level was higher, inH2-eb1-/-gene knockout mice of alergic rhinitis than those in the H2-eb1+/+ gene knockout wild-type mice. These results suggest thatH2-eb1 gene may play an important role in regulating Th1/Th2 imbalance in the pathogenesis of alergic rhinitis.
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Objective:To analyze effect on the CD154-CD40 signaling pathway and Th1/Th2 polariza-tion by deficient inducible co-stimulator ( ICOS)-ICOS ligand ( ICOSL) signaling in mice infected with Schistosoma japonicum. Methods:ICOSL knockout ( ICOSL-KO) mice and wild-type C57BL/6J mice were used as experimental Schistosomiasis model infected with Schistosoma japonicum. The expressions of CD154 and CD40 on splenocytes and on inflammatory cells around granulomatous infiltration of liver in mice infected with Schistosoma japonicum were analyzed by flow cytometry,immunohistochemical staining, respectively, on the day before infection (0 week) and at the end of 4, 7, 12, 16 and 20 weeks post-infection. The splenocytes of the mice were stimulated with soluble egg antigen( SEA) for 72 hours, then the concentrations of interferon gamma(IFN-γ) and interleukin-4 (IL-4) in the culture supernatants were measured by sandwich enzyme-linked immunosorbent assay ( ELISA) kits. The levels of SEA-specific an-tibodies of IgG and IgG1 and IgG2a were measured in the mice sera by ELISA. The granulomatous pa-thology in the mice liver was dynamically observed by hematoxylin and eosin ( HE ) staining. Results:Compared with the wild-type C57BL/6J mice, the expressions of CD154 on CD4 + T splenocytes [(18. 62 ± 4. 76)% vs. (27. 91 ± 3. 94)%, (22. 44 ± 4. 67)% vs. (40. 86 ± 5. 21)%, (25. 50 ± 6. 81)% vs. (43. 81 ± 8. 41)%, (20. 22 ± 5. 28)% vs. (40. 95 ± 7. 34)%, (17. 87 ± 4. 59)% vs. (33. 16 ± 6. 31)%, all P <0. 01] and of CD40 on CD19 + B splenocytes [(19. 43 ± 3. 26)% vs. (24.37 ±3.59)%, (23. 00 ± 4. 47)% vs. (31. 80 ± 5. 86)%, (24. 46 ± 5. 01)% vs. (35. 85 ± 5. 32)%, (23. 42 ± 4. 69)% vs. (33. 30 ± 6. 14)%, (22. 85 ± 3. 78)% vs. (30. 88 ± 5. 94)%, all P<0 . 05 ] in the ICOSL-KO mice significantly decreased at the end of 4 , 7 , 12 , 16 and 20 weeks post-infection. Moreover, the expressions of CD154[(0. 319 ± 0. 066) vs. (0. 488 ± 0. 086), (0. 389 ± 0. 067) vs.(0.596±0.082),(0.378±0.064) vs.(0.543±0.072),(0.348±0.069) vs.(0.523±0.076), all P<0. 01] and CD40[ (0. 398 ± 0. 066) vs. (0. 546 ± 0. 079), (0. 461 ± 0. 085) vs. (0. 618 ± 0. 076), (0. 453 ± 0. 087) vs. (0. 587 ± 0. 074), (0. 449 ± 0. 065) vs. (0. 565 ± 0. 082), all P <0 . 05 ] on inflammatory cells around granulomatous infiltration in liver from the ICOSL-KO mice were sig-nificantly lower than those of the wild-type C57 BL/6 J mice at the end of 7 , 12 , 16 and 20 weeks post-in-fection. The levels of IFN-γ of the ICOSL-KO mice were significantly higher than those of the wild-type C57BL/6J mice at the end of 4, 7, 12, 16 and 20 weeks post-infection (P <0. 05). However, the levels of IL-4 of the ICOSL-KO mice were significantly lower than those of the wild-type mice ( P <0. 05). Compared with the wild-type C57BL/6J mice, the levels of SEA-specific antibodies of IgG and IgG1 and IgG2a in the sera of the ICOSL-KO mice significantly decreased (P<0. 01). Moreover, The Th2 differentiation index of the ICOSL-KO mice was significantly lower than that of the wild-type mice in post-infection (P<0. 01). Also, the ratio of IgG1/IgG2a of the ICOSL-KO mice were significantly lower than that of the wild-type mice at the end of 7 , 12 and 16 weeks post-infection ( P<0 . 05 ) . And the vo-lume of liver egg granulomas of the ICOSL-KO mice was significantly smaller than that of the wild-type mice ( P <0 . 01 ) . Conclusion: These findings suggest that there is obvious down-regulation in the expressions of CD154 and CD40 and impairment of Th2 immune response in the ICOSL-KO mice infected with Schistosoma japonicum, accompanying with notedly reduced hepatic granulomatous pathology. The ICOS-ICOSL signaling has a regulatory effect on CD154-CD40 signaling pathway, and may play an impor-tant role in the hepatic egg granuloma formation of Schistosomiasis.
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Background:Dexamethasone can protect mice against the acute inflammatory liver injury by inhibiting innate immune cell function. However,the roles of T cell in this protective effect remain unknown. Aims:To investigate the regulatory effect of dexamethasone on T cell immune response in acute inflammatory liver injury. Methods:Six male C57BL/ 6J mice were randomly divided into 2 groups. One hour before induction of acute inflammatory liver injury by lipopolysaccharide, dexamethasone 5 mg/ kg and PBS were given intraperitoneally in experimental group and model group,respectively. All the mice were sacrificed 12 hours after model construction. The clinical score and liver function parameters were assessed;splenic mononuclear cells were isolated for measurements of T cell activation,as well as cytokine expression,secretion, and transcriptional factor expression for different T-cell subsets. Results:Clinical score and serum levels of transaminase were significantly lower in experimental group when compared with the model group. Meanwhile,percentage of CD44 +CD62L - T cells(i. e. activated or memory T cells)from spleen was significantly decreased in experimental group. Among splenic T cell population,expression and secretion of IFN-γ,a Th1-type cytokine,was decreased;expression and secretion of IL-4,a Th2-type cytokine,percentage of regulatory T cells(Treg cells),and ratios of Th2 / Th1 and Treg/ Th1 were increased;transcriptional factor specific for Th1 cells was down-regulated,and those for Th2 and Treg cells were up-regulated. Conclusions:Dexamethasone inhibits T cell activation and directs the reciprocal T cell lineage differentiation (repressing Th1 cell differentiation,promoting Th2 and Treg cell differentiation),which may contribute to the protection against acute inflammatory liver injury.
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Background:Faecalibacterium prausnitzii(Fp)is a commensal intestinal bacterium that exhibits anti-inflammatory and immunomodulatory capacity in vivo and in vitro. It has been reported that Fp in intestinal lumen was reduced in patients with colorectal cancer,which might be a factor associated with cancer development. Aims:To investigate the effect and immunological mechanism of Fp and its genomic DNA(fDNA)on the killing activity of peripheral blood mononuclear cells (PBMCs)against human colon cancer LoVo cells. Methods:PBMCs derived from healthy adults were co-cultured in vitro with Fp,fDNA,or the digested fDNA(d-fDNA),respectively. Killing activity of PBMCs against LoVo cells was measured by MTT assay;concentrations of interferon-gamma(INF-γ),a Th1-type cytokine and interleukin-4(IL-4),a Th2-type cytokine in culture supernatant of PBMCs were determined by ELISA;and expressions of T-bet and GATA3,the transcription factors specific for Th1 and Th2 cells,were measured by real-time PCR. Results:Compared with the PBMCs not treated,fDNA could significantly enhance the killing activity of PBMCs against LoVo cells(P < 0. 05);meanwhile,it promoted IFN-γ secretion,up-regulated T-bet mRNA expression and inhibited IL-4 secretion and GATA3 mRNA expression in PBMCs(P < 0. 05). Similar effects were not observed in PBMCs treated with Fp and d-fDNA. Conclusions:fDNA enhances the killing activity of PBMCs against human colon cancer cells by up-regulating Th1 immune response.
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Objective To investigate the therapeutic effect of CTLA4Ig gene on experimental autoimmune thyroiditis (EAT) by the use of portable synthetic costimulatory molecules of cytotoxic T lymphocyte antigen 4 (CTLA-4) antagonist (CTLA4Ig) eukaryotic expression vector.Methods Thirty C57BL/6J female mice were divided into three groups,named EAT model group (EAT,n =10),CTLA4Ig-treatment group (CTLA4Ig-EAT,n =10) and control group(n =10).At 28 day after first immunization,plasmids mixture with pCI or pCI/CTLA4Ig were injected into thyroid tissues of EAT and CTLA4Ig-EAT by surgery,respectively.Serum,thyroid tissues and spleens were collected as samples.Thyroid autoantibody and expression of interleukin (Th)1,Th2 related cytokinesby were measured by real-time quantitative PCR and ELISA.Results Compared with EAT group,the expression of CTLA-4 in thyroid of CTLA4Ig-EAT group was elevated double folds (P =0.038),and the expression of Th1 cytokine interferon γ and intercellular adhesion molecule-1 decreased significantly (P =0.016,0.042).Meanwhile,Th2 cytokine IL-4 was increased after CTLA4Ig treatment (P =0.044).The same changes were seen in spleen tissues and serum.There was no significant difference in terms of TPOAb between EAT and treated group.Conclusion Local thyroid injection of CTLA4Ig gene shows the therapeutic effect to same degree on EAT through adjusting the underlying Th1/Th2 imbalance.