Anticomplement immunofluorescence for the titration of antibody to varicella-zoster virus

Anticomplement immunofluorescence (ACIF) was tested for its use for the titration of antibody against varicella-zoster virus (VZV). ACIF antibody responses of patients with VZV infection were specific for VZV antigen and heterotypic responses to herpes simplex virus type-1 and cytomegalovirus antigens were not observed. Comparative studies of ACIF, membrane immunofluorescence (MIF) and indirect immunofluorescence (IF), using acetone-fixed antigen, were carried out with nonimmune sera and convalescent sera of patients who had recovered from varicella, herpes zoster and Rumsey Hunt disease. Nonspecific staining occurred with some nonimmune sera at a 1:4 dilution in the MIF and IF tests, after freezing and thawing of the serum, but not in the ACIF test. The antibody titers in convalescent sera agreed well in these three methods and the highest titer was obtained by MIF. The titers in ACIF and IF were similar but the ACIF antibody decreased earlier than the IF antibody during convalescence. On the other hand there was a discrepancy between the titers of ACIF and those of MIF and IF antibody in the sera of healthy adults, all sera with titers higher than 10 in the MIF and IF tests had titers below 10 in the ACIF test. The average titer of ACIF antibody declined to less than 10 with increasing age (13 to more than 20 years), whereas the MIF antibody increased during the same period of life.     

Studies on the mechanism of suppression of delayed hypersensitivity by the antischistosomal compund niridazole.

Niridazole given in a single oral dose of 100 mg/kg to guinea pigs sensitized to ortho-chlorobenzoyl chloride-bovine gamma-globulin (OCB-BGG) regularly abolished delayed cutaneous reactivity. Little effect was observed, however, when cells from these animals were tested in vitro with either direct or indirect assays for migration inhibitory factor (MIF). On the other hand, sera taken from nonsensitized guinea pigs after they had received 100 mg/kg of niridazole markedly diminished antigen-induced inhibition of migration of sensitized peritoneal exudate cells in vitro. The immunosuppressive effects of such sera could not be produced by niridazole itself, thereby suggesting an effect of niridazole metabolites. This suppressive activity was readily removed from the serum by dialysis. The active serum blocked the production of MIF by sensitized lymph node cells but did not affect the action of preformed MIF on macrophages. The effect of this serum was reversible; lymph node cells incubated for 24 hr with active serum, then washed and reincubated with antigen in normal serum, produced normal amounts of MIF. These studies suggest that metabolites of niridazole, but not the parent compound itslef, suppress delayed hypersensitivity in guinea pigs and prevent MIF production by lymphocytes without affecting the macrophage response to MIF.     

Serum gelatinases (MMP-2 and MMP-9) and VCAM-1 as a guideline in a therapeutic approach in Graves' ophthalmopathy

INTRODUCTION: The aim of this study was to estimate the influence of corticosteroids on soluble MMP-2, MMP-9 and VCAM-1 in patients with Graves ophthalmopathy (GO) in order to assess their usefulness as a guideline in a therapeutic approach. MATERIAL AND METHODS: Serum gelatinases and VCAM-1 were detected in three groups of subjects: 20 patients with GO (CAS > or = 3, anamnesis of GO > or = 1 yr), 12 patients with no clinical symptoms of ophthalmopathy (Gd) and 10 healthy volunteers. Corticosteroid therapy consisted of intravenous infusions (2 series, 3 grams each time) of methylprednisolone (MP) and subsequent treatment with oral prednisone (60 mg per day) in a tapering schedule. The serum samples were collected 24 hours before MP, 24 hours after MP, after 14 days of treatment with prednisone and at the end of corticosteroid therapy. The levels of soluble MMP-2, MMP-9 and VCAM-1 were determined by the ELISA method. RESULTS: We have found no differences in serum MMP-2 between the groups studied and a significant reduction after MP only in corticosteroid-resistant GO patients. Soluble MMP-9 was highest in the GO group compared with both the Gd and control individuals. Moreover serum MMP-9 decreased in corticosteroid-responsive GO patients after MP and remained at the lower level at the end of the study. Positive correlations between MMP-2 and MMP-9 before and after MP administration were observed. Serum VCAM-1 was significantly elevated both in GO and Gd subjects and pre-treatment VCAM-1 levels were elevated in corticosteroid-responders compared with non-responders. CONCLUSIONS: Our results suggest that serum VCAM-1 may serve as a marker predicting the efficacy of corticosteroids and that soluble MMP-9 may be helpful in monitoring corticosteroid administration and in decision-making with regard to further GO treatment.     

腹腔内贝伐珠单抗辅助卵巢癌术后化疗对患者血清AFP、VEGF、TGF-β1、MIF的影响

目的:研究腹腔内贝伐珠单抗辅助卵巢癌术后化疗对患者血清甲胎蛋白(AFP)、血管内皮生长因子(VEGF)、转化生长因子(TGF-β1)、巨噬细胞移动抑制因子(MIF)的影响。方法:选取2019年1月至2021年2月的210例卵巢癌患者。按照随机数表法分为观察组(n=101)和对照组(n=109),对照组采用化疗治疗,观察组在对照组的基础上,采用腹腔内贝伐珠单抗辅助治疗。对比两组治疗效果,血清治疗前后AFP、VEGF、TGF-β1、MIF水平变化,不良反应,随访生存分析结果。结果:治疗后,观察组总有效率显著高于对照组[89.11%(90/101)vs66.05%(72/109)](P<0.05);血清AFP、VEGF、TGF-β1、MIF水平显著低于对照组[(5.19±1.37)ng/mLvs(10.21±2.38)ng/mL,(22.61±4.32)ng/Lvs(35.76±6.34)ng/L,(168.03±20.18)ng/Lvs(203.76±28.69)ng/L,(4.81±1.01)μg/Lvs(12.79±2.50)μg/L](P<0.05);两组不良反应对比无显著差异(P>0.05);平均生存时间、2年生存率显著高于对照组[(19.23±1.36)月vs(19.23±1.36)月,79.21%(80/101)vs28.44%(31/109)](P<0.05),局部复发与转移显著低于对照组[9.90%(10/101)vs13.76%(15/109)](P<0.05)。结论:腹腔内贝伐珠单抗辅助卵巢癌术后化疗可有效改善患者的临床症状,缓解疾病发展,降低血清AFP、VEGF、TGF-β1、MIF水平,提高患者生存预后。     

The role of immunoglobulin receptors on lymphocytes in production of MIF in guinea pigs

The effect of anti-guinea pig IgG sera and anti-rabbit light kappa chain serum on the capacity of sensitized lymphocytes of guinea pigs to production of migration inhibitor factor (MIF) was investigated. The lymph node cells, thymocytes and circulating lymphocytes taken from dinitrophenyl- (DNP) sensitized guinea pigs were preincubated with antisera against gamma₁ + gamma₂ globulins, gamma₁ globulins, gamma₂ globulin, light kappa chains or normal rabbit serum as control and stimulated with antigen in vitro to production of MIF. The inhibitory effect of lymphocyte culture supernates on the migration of guinea pig normal macrophages was determined by capillary tube test. It was found that all the anti-immunoglobulin sera used suppressed, in varied degree, the release of MIF by sensitized lymphocytes. It is suggested that the suppressive influence of anti-IgG sera reflects their blocking effect on surface receptors specific for antigen.     

Characterization of the serological response to phospholipase D protein of Chlamydophila pneumoniae in patients with acute coronary syndromes

The purpose of this study was to evaluate the serological response to the recombinant phospholipase D protein of Chlamydophila pneumoniae (CpPLD) in patients with acute coronary syndromes (ACS) and infected by C. pneumoniae.We assessed 100 serum samples from ACS patients and 100 sera from healthy blood donors, all categorized by microimmunefluorescence (MIF) into subjects with presumptive C. pneumoniae infection or past exposure (only specific IgG), chronic infection (presence of specific IgG and IgA), and uninfected, unexposed subjects (MIF titer <1:32). None of the MIF-negative sera showed antibodies against CpPLD. Among MIF-positive subjects, antibodies to CpPLD were consistently found in sera of ACS patients but not in those of healthy subjects, and their titers in ACS patients were higher in subjects with both MIF IgG and IgA than in those with MIF IgG only. Additionally, we recognized an immunodominant P5 epitope in position 233–252 aa of the CpPLD protein which strongly reacted with ACS sera.These data suggest that CpPLD is a protein potentially implicated in the pathogenesis of C. pneumoniae infection. The CpPLD protein and its P5 peptide could be plausible antigens for the diagnosis of C. pneumoniae chronic infections in ACS patients.     

乙肝患者肝组织乙型肝炎病毒cccDNA和血清MIF表达的相关性研究

目的:探讨乙肝患者肝组织乙型肝炎病毒(hepatitis B virus,HBV)共价闭合环状DNA(covalently closed circular DNA,cccDNA)和血清巨噬细胞移动抑制因子(Macrophage migration inhibitory factor,MIF)的表达相关性。方法:选择2016年2月到2016年7月在我院诊治的乙肝患者144例作为乙肝组,同期选择体格检查健康者144例作为对照组,采集所有入选者的血清样本,检测血清MIF、谷丙转氨酶(Glutamic pyruvic transaminase,ALT)、谷草转氨酶(Glutamic pyruvic aminotransferase,AST)、总胆红素(total bilirubin,TBIL)的表达,并对乙肝组患者肝组织HBV cccDNA采用荧光定量PCR技术检测表达分析,直线相关分析乙肝组的血清HBV cccDNA表达量与血清ALT、TBi L、AST、MIF含量相关性。结果:乙肝组的血清MIF、ALT、TBi L、AST含量均明显高于对照组(P0.05)。乙肝组的肝组织HBV cccDNA阳性率为54.17%(78/144)。直线相关分析显示乙肝组的肝组织HBV cccDNA表达量与血清ALT、TBi L、AST、MIF含量均呈现明显正相关性(P0.05)。结论:乙肝患者体内血清MIF水平明显升高,伴肝组织HBV cccDNA的表达也升高,两者存在明显的正相关性。因此检测血清MIF水平有助于评估乙肝患者HBV的感染情况。     

Comparison of two microimmunofluorescence tests for detecting antibodies to Chlamydia pneumoniae

Two microimmunofluorescence (MIF) tests were compared for detection of antibodies to Chlamydia pneumoniae: the microimmunofluorescence of Washington University and the microimmunofluorescence of Chlamydia Serofia. Concordant positive results at the same dilution were observed for IgG in 37.33% of sera tested and concordant negative results were found in 44%. Variations of one fold dilution were observed in 36 sera. Extensive variations (2-3 two-fold dilutions) in the numeric titer values were observed in 20 serum samples with titers of antibody generally higher in the Chlamydia Serofia MIF than in the Washington MIF, resulting in a diagnosis of current infection in three patients. IgM were found with both methods only in one patient. The discrepancies observed may be due to several factors including the different TWAR strain used as antigen in the two tests and the dilution of the FITC-labelled conjugated anti-human IgG.We think that MIF serology may also be influenced by the type of response of the host that may depend on the "local strain" of C. pneumoniae that may express different antigens or in different amounts in comparison with the strains used by the commercial kit.     

The MIF Antagonist ISO-1 Attenuates Corticosteroid-Insensitive Inflammation and Airways Hyperresponsiveness in an Ozone-Induced Model of COPD

Introduction

Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine associated with acute and chronic inflammatory disorders and corticosteroid insensitivity. Its expression in the airways of patients with chronic obstructive pulmonary disease (COPD), a relatively steroid insensitive inflammatory disease is unclear, however.

Methods

Sputum, bronchoalveolar lavage (BAL) macrophages and serum were obtained from non-smokers, smokers and COPD patients. To mimic oxidative stress-induced COPD, mice were exposed to ozone for six-weeks and treated with ISO-1, a MIF inhibitor, and/or dexamethasone before each exposure. BAL fluid and lung tissue were collected after the final exposure. Airway hyperresponsiveness (AHR) and lung function were measured using whole body plethysmography. HIF-1α binding to the Mif promoter was determined by Chromatin Immunoprecipitation assays.

Results

MIF levels in sputum and BAL macrophages from COPD patients were higher than those from non-smokers, with healthy smokers having intermediate levels. MIF expression correlated with that of HIF-1α in all patients groups and in ozone-exposed mice. BAL cell counts, cytokine mRNA and protein expression in lungs and BAL, including MIF, were elevated in ozone-exposed mice and had increased AHR. Dexamethasone had no effect on these parameters in the mouse but ISO-1 attenuated cell recruitment, cytokine release and AHR.

Conclusion

MIF and HIF-1α levels are elevated in COPD BAL macrophages and inhibition of MIF function blocks corticosteroid-insensitive lung inflammation and AHR. Inhibition of MIF may provide a novel anti-inflammatory approach in COPD.     

Induction of macrophage migration inhibitory factor precedes the onset of acute tonsillitis

We investigated the serum macrophage migration inhibitory factor (MIF) levels of palmoplantar pustulosis patients, before and after the tonsillar provocation test. Higher serum MIF levels of palmoplantar pustulosis patients were decreased after the tonsillar provocation test (n=29). To confirm these phenomena, two patients with acute tonsillitis had their changes in body temperature, C-reactive protein (CRP) and serum MIF levels examined during the course of their illness. Surprisingly, increased MIF preceded fever and CRP elevation, and MIF subsequently decreased at the onset of fever and CRP elevation. Since MIF is an initiator of other proinflammatory cytokines, we suggest that the induction of MIF may precede other inflammatory conditions.     

Detection of serum antibodies against Chlamydia pneumoniae by ELISA

Abstract Chlamydia pneumoniae causes pneumonia and other respiratory infections in children, adolescents and adults. We tried to evaluate the diagnostic value of detection of serum antibodies by ELISA for C. pneumoniae infections in Japanese children. Serum IgG, IgA and IgM antibodies to C. pneumoniae were determined by the microimmunofluorescence (MIF) test. Serum IgG and IgA antibodies were also determined by ELISA test kits. Results obtained by ELISA were compared with those obtained by MIF test. IgG antibody to C. pneumoniae was detected in 135 (39.5%) by ELISA and in 125 (36.5%) by MIF out of 342 sera from Japanese infants and children without respiratory infections (aged from 2 months old to 15 years old). IgA antibody to C. pneumoniae was detected in 129 (37.7%) by ELISA and in 117 (34.2%) by MIF out of 342 sera tested. Of 342 specimens 113 were IgG-positive by ELISA and MIF (sensitivity: 90.4%, specificity: 89.9%, r = 0.853). Of 342 sera 28 had IgG antibody titers of 1:256 and none had titers 1:512 or higher by MIF. Of 28 infants and children a total of nine were less than 4 years of age. On the other hand, of 342 specimens 99 were IgA-positive by ELISA and MIF (sensitivity: 84.6%, specificity: 86.7%, r = 0.769). Of 342 sera 16 had IgA antibody titers of 1:256 or higher by MIF. Of 16 infants and children, ten were less than 4 years of age. ELISA had excellent sensitivity and specificity relative to MIF test for detection of IgC and IgA antibodies to C. pneumoniae . It was suggested that C. pneumoniae infection in Japanese infants and children under 4 years of age was not infrequent.     

D-二聚体、超敏CRP在降主动脉夹层诊断与治疗中的意义

目的:探讨D-二聚体、超敏CRP(hs-CRP)在降主动脉夹层诊断与治疗中的意义。方法:本研究入选2013年1月至2013年10月沈阳军区总医院心血管内科收治的降主动脉夹层患者80例,分别于术前、术后第1日及第3日检测所有患者的血清D-二聚体、hs-CRP水平。结果:所有入选患者术前、术后第1日及术后第3日的血清D-二聚体水平均显著高于正常参考值,且不同时期比较有统计学差异(P=0.005)。急性期患者术前、术后第1日血清D-二聚体水平均明显高于相应时期的慢性期患者(P=0.022、P=0.001)。所有患者术前、术后第1日及术后第3日的血清hs-CRP水平均高于正常参考值,但不同时期比较差异无统计学意义(P=0.812)。急性期患者术前及术后第1日血清hs-CRP水平均明显高于慢性期患者(P=0.002;P=0.002)。围手术期未出现因夹层破裂死亡病患,急性肾功能不全1例。结论:联合检测血清D-二聚体、hs-CRP水平有助于辅助诊断降主动脉夹层,且主动脉腔内隔绝术后血清D-二聚体、hs-CRP的水平可提示患者的预后。     

Tacrolimus as a Part of Immunosuppressive Treatment in Kidney Transplantation Patients: Sex Differences

BackgroundMetabolism interaction between corticosteroids and tacrolimus (Tac) exists and can be an important factor in providing rational pharmacotherapy in kidney transplantation patients. Both Tac and corticosteroids can induce adverse metabolic effects, such as hyperglycemia, post-transplantation diabetes mellitus, and dyslipidemia.ObjectiveThe main goal of this study was to detect corticosteroid dose influence on Tac level within the first 6 months of immunosuppressive therapy. The secondary goal of this research was to investigate sex differences on Tac−corticosteroid interaction. We also monitored biochemical-parameter changes, which are related to immunosuppressive treatment.MethodsThis retrospective pharmacokinetic study included 30 Serbian patients after kidney transplantation. Patients received a quaternary immunosuppressive regimen including Tac, mycophenolate, mofetil, basiliximab, and corticosteroids. To compare dose-normalized level and dose of Tac in different days after transplantation, we performed the Friedman test and Wilcoxon matched-pairs signed rank sum test. Mann-Whitney test was performed to compare differences in dose of Tac, level of Tac, and dose-normalized level of Tac between male and female patient groups. We used the Friedman test to compare biological and clinical data.ResultsObtained results show statistical significance between dose of Tac on day 180 post transplantation and dose on days 7, 14, 21, and 60 post transplantation. There was a statistical difference in dose-normalized level of Tac between days 7 and 21 post transplantation (P < 0.01), days 7 and 60 (P < 0.01), and between days 7 and 180 (P < 0.05). There is a statistical significance between male and female levels of Tac on day 21 after transplantation (P < 0.01). Significance also exists on day 60 after transplantation between male and female dose-normalized levels (P < 0.05). There is also a statistical difference in glucose, cholesterol, triglyceride, serum creatinine, and urea level and activity of alanine aminotransferase and alkaline phosphatase before and after operation.ConclusionOur study shows that dose of corticosteroid affects Tac level in kidney transplantation patients. Tac dose and level changes showed that corticosteroid−Tac interaction has more influence on male than female patients. According to biochemical monitoring, the immunosuppressive therapy used at present is quite well tolerated.     

Reversal of established rat crescentic glomerulonephritis by blockade of macrophage migration inhibitory factor (MIF): potential role of MIF in regulating glucocorticoid production

Macrophage migration inhibitory factor (MIF) is a potent pro-inflammatory cytokine that also counter-regulates glucocorticoid action. We investigated whether immunoneutralization of MIF could reverse established experimental crescentic glomerulonephritis and if this treatment could modulate endogenous glucocorticoid levels. Accelerated anti-GBM glomerulonephritis was induced in six littermate pairs of rats. Once crescentic disease was established on day 7, one animal in each pair was given a daily injection of neutralizing anti-MIF antibody (Ab) or irrelevant isotype control Ab for 14 days and then killed on day 21. In addition, a group of 6 animals was killed on day 7 of disease without any treatment. Animals receiving the control Ab exhibited a rapidly progressive glomerulonephritis with severe renal injury (proteinuria), loss of renal function (creatinine clearance), anemia, and marked histologic damage (including glomerular crescent formation), compared with animals killed on day 7 without treatment. In contrast, anti-MIF Ab treatment partially reversed the disease by restoring normal renal function and reducing histological damage compared with untreated animals killed on day 7 (p < 0.05). Interestingly, anti-MIF Ab treatment also prevented severe anemia (p < 0.05). Reversal of disease was associated with a significant reduction in leukocyte infiltration and activation and renal interleukin-1 (IL-1) production. Importantly, anti-MIF Ab treatment caused a significant increase in endogenous serum corticosterone levels, which correlated with the reversal of disease parameters. In conclusion, this study has demonstrated that blocking MIF activity can partially reverse established crescentic glomerulonephritis and suggests that MIF operates by both enhancing the cellular immune response and suppressing the endogenous anti-inflammatory glucocorticoid response.     

Elevated Serum Levels of Macrophage Migration Inhibitory Factor Are Associated with Progressive Chronic Cardiomyopathy in Patients with Chagas Disease

Clinical symptoms of chronic Chagas disease occur in around 30% of the individuals infected with Trypanosoma cruzi and are characterized by heart inflammation and dysfunction. The pathogenesis of chronic chagasic cardiomyopathy (CCC) is not completely understood yet, partially because disease evolution depends on complex host-parasite interactions. Macrophage migration inhibitory factor (MIF) is a pleiotropic proinflammatory cytokine that promotes numerous pathophysiological processes. In the current study, we investigated the link between MIF and CCC progression.Immunohistochemical analysis demonstrated MIF overexpression in the hearts from chronically T. cruzi-infected mice, particularly those showing intense inflammatory infiltration. We also found that MIF exogenously added to parasite-infected murine macrophage cultures is capable of enhancing the production of TNF-α and reactive oxygen species, both with pathogenic roles in CCC. Thus, the integrated action of MIF and other cytokines and chemokines may account for leukocyte influx to the infected myocardium, accompanied by enhanced local production of multiple inflammatory mediators. We further examined by ELISA the level of MIF in the sera from chronic indeterminate and cardiomyopathic chagasic patients, and healthy subjects. CCC patients displayed significantly higher MIF concentrations than those recorded in asymptomatic T. cruzi-infected and uninfected individuals. Interestingly, increased MIF levels were associated with severe progressive Chagas heart disease, in correlation with elevated serum concentration of high sensitivity C-reactive protein and also with several echocardiographic indicators of left ventricular dysfunction, one of the hallmarks of CCC. Our present findings represent the first evidence that enhanced MIF production is associated with progressive cardiac impairment in chronic human infection with T. cruzi, strengthening the relationship between inflammatory response and parasite-driven pathology. These observations contribute to unravel the elements involved in the pathogenesis of CCC and may also be helpful for the design of novel therapies aimed to control long-term morbidity in chagasic patients.     

降钙素原在重症腹膜炎患者中的应用

目的:探讨降钙素原(PCT)在重症腹膜炎早期诊断和治疗效果判断中的临床意义。方法:选取2011年3月至2014年9月本院就诊的128例重症腹膜炎患者作为治疗组,并选取同期来我院体检的健康志愿者128例作为对照组,比较治疗组和对照组之间PCT水平;通过治疗后,比较好转组和恶化组患者之间PCT水平的差异。结果:治疗组患者治疗后各时段的PCT水平均显著高于对照组,差异有统计学意义(P0.05),治疗组患者的血清PCT水平在治疗后第1 d开始下降,于第1-3 d PCT水平下降速度较快,之后下降速度减缓。两组患者治疗后各时段PCT水平明显低于治疗前,且差异均具有统计学意义(P0.05)。好转组患者治疗后各时段PCT水平显著低于恶化组患者,差异具有统计学意义(P0.05),其中好转组患者血清PCT水平在治疗后第1 d开始下降,恶化组患者血清PCT水平在治疗后第1 d开始升高。与治疗前相比,好转组患者治疗后各时段PCT水平明显下降,而恶化组患者治疗后各时段PCT水平显著上升,且差异均具有统计学意义(P0.05)。结论:PCT水平不仅是重症腹膜炎的一个重要指示物,也是治疗效果的一个有效指标。     

Serum Th1 and Th2 profile cytokine level changes in patients with Graves' ophthalmopathy treated with corticosteroids.

The aim of this study was to estimate the influence of corticosteroids on Th1 and Th2 serum cytokine balance in patients with GO: IFNgamma, TNFalpha, IL-4 and IL-10. Further, we tested the hypothesis of an up-regulation of Th2 immune response during successful treatment with corticosteroids to explain their beneficial effect in Graves' ophthalmopathy. Serum cytokines were detected in three groups of subjects: 20 patients with Graves' disease without ophthalmopathy (Gd), 16 patients with clinical symptoms of ophthalmopathy (GO) (CAS over 3 points, last consultation record for GO less than a year old) and 16 healthy volunteers. Corticosteroid therapy consisted of intravenous infusions of methylprednisolone (MP) (2 series, 3 g each time) and subsequent treatment with oral prednisone (60 mg per day) in a tapering schedule. The serum samples were collected 24 hours before MP, 24 hours after MP, 14 days of treatment with prednisone and at the end of corticosteroid therapy. The levels of IFNgamma, TNFalpha, IL-4 and IL-10 in the serum were determined using ELISA. Statistical significance was estimated by the Mann-Whitney U-test. Our findings show a deviation to systemic Th2 profile cytokines in Graves' disease. In patients with GO, we found a significantly increased serum IL-10 concentration. In corticosteroid-responsive patients, the balance of serum cytokines IL-4/IFNgamma, IL-4/TNFalpha, IL-10/IFNgamma and IL-10/TNFalpha increased and remained upregulated until the end of the study. In non-responders, the balance of serum cytokines studied increased after methylprednisolone but declined markedly during continuation of the therapy with prednisone. In summary, our results show that efficient corticosteroid therapy may be related to its influence on Th2/Th1 profile cytokine balance. The upregulation of serum IL-4 and IL-10 during successful treatment with corticosteroids indicate the possibility of using these cytokines as predictors of the beneficial effect of corticosteroids in Graves' ophthalmopathy.     

Upregulation of macrophage migration inhibitory factor (MIF) and CD74, receptor for MIF, in rat bladder during persistent cyclophosphamide-induced inflammation

The objective of this study was to determine if macrophage migration inhibitory factor (MIF) is upregulated in the bladder during persistent cystitis. MIF is a pro-inflammatory cytokine found pre-formed in the urothelium. Previous findings showed that acute bladder inflammation increased MIF release into the bladder lumen while upregulating MIF and CD74 (MIF receptor) in the bladder. Because the effects of persistent cystitis on MIF and CD74 are not known, MIF and CD74 changes in the bladder were examined after short-term (1-day) or persistent (8-day) cyclophosphamide (CYP)-induced bladder inflammation. Anesthetized male Sprague-Dawley rats received either a single CYP treatment (150 mg/kg, ip; saline, control) and examined 1 day after treatment (short-term), or repeated CYP doses (20-75 mg/ kg, ip; saline, control; every third day for 8 days) and examined after 8 days of treatment (persistent). MIF protein levels in urine and bladder were determined. In addition, Mif, CD74, and cox-2 expression in the bladder was determined. Histology verified cystitis and MIF and CD74 immunoreactivity in the bladder. Repeated CYP doses were decreased to avoid toxicity. Short-term or repeated low CYP doses (40 mg/kg; 8 days) increased urinary MIF and decreased bladder MIF amounts while upregulating bladder Mif and CD74 mRNA expression. Persistent CYP-induced bladder inflammation (even at 40 mg/kg; 8-day treatment) also upregulated other inflammatory cytokines (CCL5, IL-11, iNOS) in the bladder. Short-term and persistent (low dose) CYP cystitis are associated with markedly increased MIF release into the urine and upregulation of Mif and CD74 in bladder. This supports the hypothesis that MIF and CD74 play a significant role in both acute and persistent stages of bladder inflammation.     

孕酮对外伤性蛛网膜下腔出血患者早期MMP-9水平及微循环的影响

目的:探究孕酮对外伤性蛛网膜下腔出血患者早期MMP-9水平及微循环的影响。方法:收集我院神经外科收治的外伤性蛛网膜下腔出血患者70例,根据随机数字对照表分为对照组(35例)与试验组(35例)。两组均给予常规治疗,对照组患者给予静脉注射尼莫地平治疗,试验组在此基础上给予复方甲地孕酮治疗。观察并比较两组患者治疗前后格拉斯哥昏迷指数GCS评分、金属基质蛋白酶-9(MMP9)水平及微循环的变化情况。结果:两组患者入院时GCS评分、血清MMP-9水平无明显差异(P0.05),对照组治疗14天后GCS评分明显升高(P0.05),而试验组治疗7天、14天后均明显升高(P0.05),且试验组治疗7天、14天后GCS评分较对照组评分高(P0.05);两组患者治疗7天后血清MMP-9水平降低(P0.05),且试验组血清MMP-9水平较对照组降低(P0.05);两组患者治疗后微循环均有所改善,伤测大脑中动脉收缩峰流速降低(P0.05),试验组改善更为明显,伤测大脑中动脉收缩峰流速降低更为显著(P0.05)。结论:孕酮对外伤性蛛网膜下腔出血患者的治疗效果明显,可能与其改善微循环,降低血清MMP-9水平有关。