1.Effects of erythropoietin pretreatment on pro-and anti-inflammatory balance in rats with severe acute pancreatitis.
Jiexing LI ; Yuhong LUO ; Zhendong LI ; Yong LIU ; Zhaoxiang LIU
Journal of Southern Medical University 2012;32(1):93-96
OBJECTIVETo evaluate the effect of pretreatment with erythropoietin (EPO) on disordered pro- and anti- inflammatory balance in rats with severe acute pancreatitis (SAP) and explore the underlying mechanisms.
METHODSNinety healthy male SD rats were randomized equally into sham-operated group, SAP group and EPO pretreatment group. SAP model was induced in the latter two groups by retrograde injection of 1 ml/kg 3.5% sodium traurocholate into the biliopancreatic duct. In EPO group, 3000 U/kg EPO (1000 U/ml) was administered intravenously 1 h before SAP, and normal saline was administered in the other two groups. Serum amylase activity, interleukin-10 (IL-10)and IL-18 levels were measured at different time points after the operation. The translocation and activation of nuclear factor-κB (NF-κB) in the pancreatic tissue was detected using immunofluorescence staining, and pancreatic pathologies were evaluated.
RESULTSCompared with SAP group, EPO group showed a markedly decreased activation rate of NF-κB after SAP except for 12 h (P<0.05), significantly decreased serum amylase activity at 3, 6, and 12 h (P<0.05) and decreased serum IL-18 levels at 3, 6, 24 h (P<0.05), whereas serum IL-10 underwent no significant changes. The rats in EPO group showed an obviously milder pancreatic pathology than those in SAP group at 6, 12, and 24 h (P<0.05).
CONCLUSIONEPO can effectively inhibit NF-κB activation by regulating the inflammatory mediators and restoring the pro-and anti-inflammatory balance to alleviate SAP in rats.
Acute Disease ; Animals ; Cytokines ; metabolism ; Erythropoietin ; therapeutic use ; Interleukin-10 ; metabolism ; Interleukin-18 ; metabolism ; Male ; NF-kappa B ; metabolism ; Pancreatitis ; drug therapy ; Rats ; Rats, Sprague-Dawley
2.Therapeutic efficacy and mechanisms of quercetin in a rat model of nonalcoholic fatty liver disease.
Dong-sheng ZHOU ; Zhi-qing LIANG ; Qing QIN ; Mao-hua ZHANG ; Sheng-lian LI
Chinese Journal of Hepatology 2013;21(2):134-137
OBJECTIVETo determine the efficacy of the plant-derived bioflavonoid, quercetin, for treating nonalcoholic fatty liver disease (NAFLD) by using a rat model, and to investigate the molecular mechanism underlying its therapeutic effects.
METHODSOne-hundred Sprague-Dawley rats were randomly assigned into the normal control group (normal group), untreated NAFLD model control group (model group), 75 mg/kg/day quercetin treatment group (low-dose group), and 300 mg/kg/day quercetin treatment group (high-dose group). The NAFLD rat model was established by providing four weeks of a high-fat diet; the normal group received normal rat chow diet. The quercetin treatments were administered for eight weeks after model establishment and control groups received simultaneous gavages of isotonic saline, with continuation of the respective diets. At the end of the eight weeks (experimental week 12), the rats were sacrificed for liver and serum collection. Intergroup differences in liver index, fasting blood glucose (FBG), triglycerides (TG), interleukin (IL)-18, IL-10, malondialdehyde (MDA), and histopathological features were assessed by independent samples t-test (normal vs. model), one-way ANOVA (model vs. treatments), and least significant difference t-test (pairwise comparisons); correlations were assessed by Pearson's correlation coefficient.
RESULTSCompared with the normal group, the model group showed significantly higher liver index (t=-2.327), FBG (t=-3.482), TG (t=-0.302), and serum IL-18 (t=-2.704) (all P less than 0.05), but significantly lower IL-10 (t=2.622, P less than 0.05); the MDA level was also higher in the model group, but the difference was not significant (t=-1.083, P less than 0.05). Livers from the model group showed obvious histological features of inflammation (lymphocyte and neutrophil infiltration) and steatosis (cytoplasmic lipid droplets). Inflammation was positively correlated with IL-18 (P less than 0.05), but negatively correlated with IL-10 (P less than 0.05), while steatosis was negatively correlated with IL-10 (P less than 0.05). Compared to the model group, quercetin treatment (both low- and high-dose) led to significant decreases in the liver index, FBG and IL-18 (all, P less than 0.01), and significant increase in IL-10 (P less than 0.05); however, the changes in liver index, FBG and IL-10 were not significantly different between the low- and high-dose treatment groups, but the high-dose of quercetin did induce a significantly greater decrease in IL-18 than the low-dose (P less than 0.05).
CONCLUSIONNAFLD rats have higher serum levels of IL-18 but lower levels of IL-10 than their healthy counterparts, and these differential cytokine expressions may be related to liver inflammation and steatosis. Quercetin treatment may help to delay the progression of NAFLD, possibly by adjusting the balance of inflammatory cytokines.
Animals ; Fatty Liver ; blood ; drug therapy ; Interleukin-10 ; blood ; Interleukin-18 ; blood ; Male ; Non-alcoholic Fatty Liver Disease ; Quercetin ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley
3.Clinical observation of serum IL-18, IL-10 and sIL-2R levels in patients with chronic hepatitis C pre- and post antiviral treatment.
Hongyu JIA ; Jie DU ; Sihe ZHU ; Yingji MA ; Huafeng CAI
Chinese Medical Journal 2003;116(4):605-608
OBJECTIVETo discuss the roles of serum interleukin-18 (IL-18), interleukin-10 (IL-10) and soluble interleukin-2R (sIL-2R) in the pathogenesis of chronic hepatitis C and to observe the effects of interferon (IFN) on the above- mentioned serum cytokines.
METHODSThe levels of above- mentioned cytokines were detected in 10 healthy individuals, 24 asymptomatic hepatitis virus C (HCV) carriers and 27 patients with chronic hepatitis C (before and after IFN treatment) using enzyme linked immunosorbent assay (ELISA).
RESULTSThe levels of the cytokines in patients with chronic hepatitis C are higher than in healthy people (P < 0.05) and in asymptomatic HCV carriers (P < 0.05). The values of the cytokines show a significant positive correlation to ALT (P < 0.05). Levels of tested cytokines decreased observably after IFN treatment (P < 0.05). The grades of the serum levels for sIL-2R and IL-10 before IFN treatment (from high to low) were categorized accordingly: non-response group > partial- response group > complete- response group (P < 0.05).
CONCLUSIONSThe tested cytokines co-participate in the pathogenesis of chronic hepatitis C, and can be used to evaluate the effect of IFN on the immune state of organisms. Furthermore, sIL-2R and IL-10 are important for predicting the anti-viral efficacy of IFN.
Adolescent ; Adult ; Antiviral Agents ; therapeutic use ; Female ; Hepatitis C, Chronic ; blood ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Interleukin-10 ; blood ; Interleukin-18 ; blood ; Male ; Middle Aged ; Receptors, Interleukin-2 ; blood ; Recombinant Proteins
4.Protective effect of recombinant Schistosoma japonicum cystatin against acute kidney injury associated with acute liver failure in mice.
Y XUE ; X YANG ; H ZHANG ; T ZHANG ; W CHEN ; X CHANG ; Y WANG
Chinese Journal of Schistosomiasis Control 2023;35(4):331-339
OBJECTIVE:
To evaluate the protective effect of recombinant Schistosoma japonicum cystatin (rSj-Cys) against acute kidney injury induced by acute liver failure and unravel the underlying mechanism, so as to provide insights into the clinical therapy of acute kidney injury.
METHODS:
Twenty-four male C57BL/6J mice at ages of 6 to 8 weeks were randomly divided into the normal control group, rSj-Cys control group, lipopolysaccharide (LPS)/D-galactosamine (D-GaIN) model group and LPS/D-GaIN + rSj-Cys treatment group, of 6 mice each group. Mice in the LPS/D-GaIN group and LPS/D-GaIN + rSj-Cys group were intraperitoneally injected with LPS (10 μg/kg) and D-GaIN (700 mg/kg), and mice in the LPS/D-GaIN + rSj-Cys group were additionally administered with rSj-Cys (1.25 mg/kg) by intraperitoneal injection 30 min post-modeling, while mice in the rSj-Cys group were intraperitoneally injected with rSj-Cys (1.25 mg/kg), and mice in the normal control group were injected with the normal volume of PBS. All mice were sacrificed 6 h post-modeling, and mouse serum and kidney samples were collected. Serum creatinine (Cr) and urea nitrogen (BUN) levels were measured, and the pathological changes of mouse kidney specimens were examined using hematoxylin-eosin (HE) staining. Serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were detected using enzyme-linked immunosorbent assay (ELISA), and the expression of inflammatory factors and pyroptosis-related proteins was quantified in mouse kidney specimens using immunohistochemistry. In addition, the expression of pyroptosis-related proteins and nuclear factor-kappa B (NF-κB) signaling pathway-associated proteins was determined in mouse kidney specimens using Western blotting assay.
RESULTS:
HE staining showed no remarkable abnormality in the mouse kidney structure in the normal control group and the rSj-Cys control group, and renal tubular injury was found in LPS/D-GaIN group, while the renal tubular injury was alleviated in LPS/D-GaIN+rSj-Cys treatment group. There were significant differences in serum levels of Cr (F = 46.33, P < 0.001), BUN (F = 128.60, P < 0.001), TNF-α (F = 102.00, P < 0.001) and IL-6 (F = 202.10, P < 0.001) among the four groups, and lower serum Cr [(85.35 ± 32.05) μmol/L], BUN [(11.90 ± 2.76) mmol/L], TNF-α [(158.27 ± 15.83) pg/mL] and IL-6 levels [(56.72 ± 4.37) pg/mL] were detected in the in LPS/D-GaIN + rSj-Cys group than in the LPS/D-GaIN group (all P values < 0.01). Immunohistochemical staining detected significant differences in TNF-α (F = 24.16, P < 0.001) and IL-10 (F = 15.07, P < 0.01) expression among the four groups, and lower TNF-α [(106.50 ± 16.57)%] and higher IL-10 expression [(91.83 ± 5.23)%] was detected in the LPS/D-GaIN + rSj-Cys group than in the LPS/D-GaIN group (both P values < 0.01). Western blotting and immunohistochemistry detected significant differences in the protein expression of pyroptosis-related proteins NOD-like receptor thermal protein domain associated protein 3 (NLRP3) (F = 24.57 and 30.72, both P values < 0.001), IL-1β (F = 19.24 and 22.59, both P values < 0.001) and IL-18 (F = 16.60 and 19.30, both P values < 0.001) in kidney samples among the four groups, and lower NLRP3, IL-1β and IL-18 expression was quantified in the LPS/D-GaIN + rSj-Cys treatment group than in the LPS/D-GaIN group (P values < 0.05). In addition, there were significant differences in the protein expression of NF-κB signaling pathway-associated proteins p-NF-κB p-P65/NF-κB p65 (F = 71.88, P < 0.001), Toll-like receptor (TLR)-4 (F = 45.49, P < 0.001) and p-IκB/IκB (F = 60.87, P < 0.001) in mouse kidney samples among the four groups, and lower expression of three NF-κB signaling pathway-associated proteins was determined in the LPS/D-GaIN + rSj-Cys treatment group than in the LPS/D-GaIN group (all P values < 0.01).
CONCLUSIONS
rSj-Cys may present a protective effect against acute kidney injury caused by acute liver failure through inhibiting inflammation and pyroptosis and downregulating the NF-κB signaling pathway.
Mice
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Male
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Animals
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Interleukin-10
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Tumor Necrosis Factor-alpha/genetics*
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NF-kappa B/therapeutic use*
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Interleukin-18/therapeutic use*
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Schistosoma japonicum/metabolism*
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Interleukin-6/therapeutic use*
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Lipopolysaccharides/therapeutic use*
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NLR Family, Pyrin Domain-Containing 3 Protein
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Mice, Inbred C57BL
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Acute Kidney Injury/drug therapy*
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Liver Failure, Acute
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Cystatins/therapeutic use*
5.Clinical study on treatment of recurrent genital herpes by Huangqi Fuzheng Decoction.
Yong-Jian SHI ; Xi-Xian DU ; Chun-Hong ZHANG
Chinese Journal of Integrated Traditional and Western Medicine 2008;28(3):222-224
OBJECTIVETo observe the clinical efficacy of Huangqi Fuzheng Decoction (HQFZD) in treating recurrent genital herpes (RGH) and its influence on related cytokines in peripheral blood.
METHODSEighty-four patients with RGH were randomly assigned to 3 groups, the treated group treated with HQFZD (31 cases), the control group A (25 cases) treated with Aciclovir, and the control group B (28 cases) treated with Aciclovir plus interferon. The course of treatment was 3 weeks for all. The relapse rate was estimated at 6 months after treatment, and levels of IL-4, IL-10, IL-12 and IL-18 in all patients were detected before and after treatment using double-sandwich ELISA.
RESULTSAll patients were cured after treatment. The relapse rate in the treated group and the control group B was lower than that in the control group A (P < 0.01) but insignificant difference was shown between the former two groups. Before treatment, patients' serum levels of IL-4 and IL-10 were significantly higher while those of IL-12 and IL-18 were lower than the normal range (P < 0.01). The abnormal change aforementioned reversed after treatment in the treated group and the control group B (P < 0.05 or P < 0.01), showing a superior effect to that in the control group A (P < 0.01).
CONCLUSIONHQFZD can reduce the relapse rate of RGH without obvious adverse reaction, and it could also enhance the immunity of the patients.
Adolescent ; Adult ; Cytokines ; blood ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Herpes Genitalis ; blood ; drug therapy ; pathology ; Humans ; Interleukin-10 ; blood ; Interleukin-12 ; blood ; Interleukin-18 ; blood ; Interleukin-4 ; blood ; Male ; Middle Aged ; Phytotherapy ; Recurrence ; Young Adult
6.Effects of recombinant fusion protein interleukin-18 on expression of immune-inflammatory factors in mice infected with Staphylococcus aureus.
Chen CHEN ; Qiang CHEN ; Lan LI ; Xiao-Jun YU ; Jiang-Wei KE ; Mei-Juan HE ; Hong-Ping ZHOU ; Wen-Ping YANG ; Wen-Xing WANG
Chinese Journal of Contemporary Pediatrics 2017;19(6):705-711
OBJECTIVETo observe the effects of recombinant fusion protein interleukin (IL)-18 on the expression of immune-inflammatory factors in the mice infected with Staphylococcus aureus (SA), and to investigate the mechanism of action of IL-18 in defense of SA infection in vivo.
METHODSA total of 40 specific pathogen-free female BLAB/c mice were randomly divided into four groups: control, SA infection, immunized, and intervention. A mouse model of SA infection was established by nasal inoculation with SA liquid. The immunized group and the intervention group were intranasally given IL-18 before SA modeling, and then the SA infection group and the intervention group received the nasal inoculation with SA liquid; the control group was treated with phosphate buffered saline instead. The levels of IL-4, interferon (IFN)-γ, tumor necrosis factor (TNF), granulocyte colony-stimulating factor (G-CSF), IgM in the serum and bronchoalveolar lavage fluid (BALF) of mice were measured by enzyme-linked immunosorbent assay. The expression of macrophage inflammatory protein (MIP)-1α mRNA and MIP-2β mRNA in the lung tissue of mice were determined by real-time fluorescent quantitative PCR.
RESULTSCompared with the control group, the SA infection group and the immunized group had significantly higher levels of IL-4, G-CSF, and IgM in the serum and BALF and expression of MIP-1α mRNA and MIP-2β mRNA in the lung tissue (P<0.05); the SA infection group had a significantly lower level of IFN-γ and a significantly higher level of TNF in the serum and BALF (P<0.05); the immunized group had a significantly higher level of IFN-γ in the serum and BALF (P<0.05). Compared with the SA infection group, the intervention group had significantly higher levels of IL-4, IFN-γ, G-CSF, and IgM in the serum and BALF and expression of MIP-1α mRNA in the lung tissue. In contrast, the intervention group showed a significantly lower level of TNF in the serum and BALF and expression of MIP-2β mRNA in the lung tissue (P<0.05). All the above indicators in the intervention group were significantly higher than those in the control group (P<0.05), except the serum level of IFN-γ.
CONCLUSIONSIn the mice infected with SA, the recombinant fusion protein IL-18 by mucosal immunity can affect inflammatory factors in the serum and BALF and the expression of MIP-1α mRNA and MIP-2β mRNA in the lung tissue to promote the anti-infective immune response and enhance the ability to clear pathogens.
Animals ; Chemokine CCL3 ; analysis ; Female ; Granulocyte Colony-Stimulating Factor ; blood ; Interferon-gamma ; blood ; Interleukin-18 ; therapeutic use ; Interleukin-4 ; blood ; Mice ; Mice, Inbred BALB C ; Recombinant Fusion Proteins ; pharmacology ; therapeutic use ; Staphylococcal Infections ; drug therapy ; immunology
8.Leihong granule intervened in-stent restenosis after endovascular therapy for lower extremity arterial occlusive diseases: a clinical observation.
Bing HAN ; Chang-Qing GE ; Li-Pu WANG ; Su-Fei ZHANG ; Heng-Zhou LI ; Hong-Guang ZHANG ; Chen-Guang ZHOU ; Guo-Hui JI ; Zheng YANG ; Liang ZHANG
Chinese Journal of Integrated Traditional and Western Medicine 2014;34(2):153-156
OBJECTIVETo observe the intervention effect of Leihong Granule (LG) in in-stent restenosis (ISR) after endovascular therapy for lower extremity arterial occlusive diseases (LEAOD).
METHODSRecruited 80 LEAOD patients who successfully underwent endovascular therapy (balloon dilation and stent implantation) were randomly assigned to two groups, the control group and the LG group, 40 in each group. Patients in the control group received basic treatment, while those in the LG group additionally took LG for 3 months. Plasma levels of IL-10, IL-18, CRP, and the intima-media thickness (IMT) of lower extremity artery were observed in the two groups between and after treatment. The rate of stent patency, ABI, intermittent claudication, rest pain, and the incidence of amputation the two groups were recorded and observed in the two groups.
RESULTSIn the control group, serum levels of IL-10, IL-18, CRP, and IMT were significantly higher one month after surgery than before surgery (P < 0.05). There was no significant difference in serum levels of IL-10, IL-18, CRP, or IMT between the two groups before surgery (P > 0.05). These indices were obviously lower in the LG group than in the control group after surgery (P < 0.05). Compared with the control group, the incidence rates of intermittent claudication and the rest pain at 6 months and 12 months after surgery significantly decreased (P < 0.05). The stent patency rate at 6 months and 12 months after surgery, and ABI were significantly higher than those of the control group (P < 0.05). There was no statistical difference in the amputation rate between the two groups (P > 0.05).
CONCLUSIONLG might effectively improve ischemic symptoms of affected limbs possibly through lowering the ISR rate after endovascular therapy for LEAOD through preventing immunosuppressive actions.
Aged ; Aged, 80 and over ; Arterial Occlusive Diseases ; therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Graft Occlusion, Vascular ; therapy ; Humans ; Interleukin-10 ; blood ; Interleukin-18 ; blood ; Lower Extremity ; blood supply ; Male ; Middle Aged ; Phytotherapy ; Stents ; Treatment Outcome
10.Molecular regulative mechanisms of NLRP3 inflammasome activation in diabetic nephropathy and interventional effects of Chinese herbal medicine.
Wen-Wen WANG ; Wen-Bei HAN ; Yi-Gang WAN ; Yue TU ; Bu-Hui LIU ; Ying-Lu LIU ; Wei WU ; Hong-Yun YEE ; Qi-Jun FANG ; Jian YAO
China Journal of Chinese Materia Medica 2020;45(1):7-13
The progression of renal damage in diabetic nephropathy(DN)is closely related to Nod-like receptor protein3(NLRP3)inflammasome activation. The characteristics of NLRP3 inflammasome activation include the changed expression and combination levels of NLRP3, apoptosis-associated speck-like protein(ASC)and pro-caspase-1, the increased expression levels of caspase-1, interleukin(IL)-1β and IL-18 and the excessive release levels of the relative inflammatory mediators. Its molecular regulative mechanisms involve the activation of multiple signaling pathways including reactive oxygen species(ROS)/thioredoxin-interacting protein(TXNIP)pathway, nuclear factor(NF)-κB pathway, nuclear factor erythroid-related factor 2(Nrf2)pathway, long non-coding RNA(lncRNA)pathway and mitogen-activated protein kinases(MAPKs)pathway. In addition, more importantly, never in mitosis aspergillus-related kinase 7(Nek7), as a kinase regulator, could target-combine with NLRP3 at upstream to activate NLRP3 inflammasome. Some extracts of Chinese herbal medicines(CHMs)such as quercetin, curcumin, cepharanthine, piperine and salidroside, as well as Chinese herbal compound prescriptions such as Wumei Pills both could treat NLRP3 inflammasome to ameliorate inflammatory renal damage in DN. Therefore, accurately clarifying the targets of anti-inflammatory CHMs and Chinese herbal compound prescriptions delaying DN progression by targeting the molecular regulative mechanisms of NLRP3 inflammasome activation will be one of the development directions in the future.
Caspase 1/immunology*
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Diabetes Mellitus/drug therapy*
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Diabetic Nephropathies/immunology*
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Drugs, Chinese Herbal/therapeutic use*
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Humans
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Inflammasomes/immunology*
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Interleukin-18/immunology*
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Interleukin-1beta/immunology*
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NIMA-Related Kinases
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NLR Family, Pyrin Domain-Containing 3 Protein/immunology*