急性心肌梗死病人血浆巨噬细胞移动抑制因子水平变化的研究

目的 :研究急性心肌梗死 (AMI)病人血浆巨噬细胞移动抑制因子 (MIF)水平变化的特征。方法 :征集完全符合诊断标准的AMI病人 37例 ,不稳定型心绞痛 (UA)病人 2 6例 ,稳定型心绞痛 (SA)病人 39例 ,接受经皮腔内冠状动脉成形术(PTCA)病人 2 6例 ,有非典型胸痛而冠状动脉造影正常的对照组 31例。这几组病人分别在发病第 1,2 ,3天抽取血样 ,用酶联免疫吸附试验 (ELISA)检测MIF水平 ,用贝克曼生化仪检测心肌酶的水平。结果 :在发病第 1～ 3天 ,AMI病组与SA组、UA组、PTCA组、对照组等比较 ,AMI病组血浆MIF水平明显高于其它病组 ,差异具有显著性 (P <0 0 0 1)。在发病第 1,2天 ,其MIF水平变化量的差异也具有显著性 (P <0 0 5 )。结论 :血浆MIF升高不仅可反映AMI病人病情的严重性 ,而且在预测AMI早期的潜在危险性方面具有重要作用     

Glucocorticoids and macrophage migration inhibitory factor (MIF) are neuroendocrine modulators of inflammation and neuropathic pain after spinal cord injury

Traumatic spinal cord injury (SCI) activates the hypothalamic–pituitary–adrenal (HPA) axis, a potent neuroendocrine regulator of stress and inflammation. SCI also elicits a profound and sustained intraspinal and systemic inflammatory response. Together, stress hormones and inflammatory mediators will affect the growth and survival of neural and non-neural cells and ultimately neurologic recovery after SCI. Glucocorticoids (GCs) are endogenous anti-inflammatory steroids that are synthesized in response to stress or injury, in part to regulate inflammation. Exogenous synthetic GCs are often used for similar purposes in various diseases; however, their safety and efficacy in pre-clinical and clinical SCI is controversial. The relatively recent discovery that macrophage migration inhibitory factor (MIF) is produced throughout the body and can override the anti-inflammatory effects of GCs may provide unique insight to the importance of endogenous and exogenous GCs after SCI. Here, we review both GCs and MIF and discuss the potential relevance of their interactions after SCI, especially their role in regulating maladaptive mechanisms of plasticity and repair that may contribute to the onset and maintenance of neuropathic pain.     

Blockade of macrophage migration inhibitory factor (MIF) prevents the antigen-induced response in a murine model of allergic airway inflammation

Objective and Design: The role of macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, was tested using a mouse asthma model. Materials: One hundred and four male BALB/c mice were used in this study. Treatment: Mice were actively sensitized with an intraperitoneal injection of ovalbumin (OVA) and challenged with repeated nebulization of 1 w/v% OVA. Polyclonal anti-MIF antibody was intraperitoneally injected at 10 mg/kg during the antigen challenge period. Methods: Bronchoalveolar lavage (BAL) was performed 8 h after the last challenge. Airway hyperresponsiveness to inhaled methacholine was measured 24 h after the last challenge. Results: Antigen challenge to immunized mice induced increase in inflammatory cells and concentration of Th2 cytokines in BAL fluid (BALF), and caused the development of airway hyperresponsiveness. Anti-MIF antibody significantly decreased the numbers of inflammatory cells including macrophages, eosinophils, lymphocytes and neutrophils in BALF from OVA-challenged mice. Prednisolone decreased the numbers of eosinophils, lymphocytes and neutrophils but not macrophages. Anti-MIF antibody reduced airway hyperresponsiveness. Anti-MIF antibody affected neither the cytokine levels in BALF nor the IgE levels in serum. Conclusion: MIF was involved in the antigen-induced inflammatory cell accumulation in the lung and airway hyperresponsiveness without affecting immune responses. Received 17 November 2005; returned for revision 14 June 2006; accepted by M. Katori 25 July 2006     

The involvement of multiple thrombogenic and atherogenic markers in premature coronary artery disease

OBJECTIVE:

To examine the association of atherogenic and thrombogenic markers and lymphotoxin-alfa gene mutations with the risk of premature coronary disease.

METHODS:

This cross-sectional, case-control, age-adjusted study was conducted in 336 patients with premature coronary disease (<50 years old) and 189 healthy controls. The control subjects had normal clinical, resting, and exercise stress electrocardiographic assessments. The coronary disease group patients had either angiographically documented disease (>50% luminal reduction) or a previous myocardial infarction. The laboratory data evaluated included thrombogenic factors (fibrinogen, protein C, protein S, and antithrombin III), atherogenic factors (glucose and lipid profiles, lipoprotein(a), and apolipoproteins AI and B), and lymphotoxin-alfa mutations. Genetic variability of lymphotoxin-alfa was determined by polymerase chain reaction analysis.

RESULTS:

Coronary disease patients exhibited lower concentrations of HDL-cholesterol and higher levels of glucose, lipoprotein(a), and protein S. The frequencies of AA, AG, and GG lymphotoxin-alfa mutation genotypes were 55.0%, 37.6%, and 7.4% for controls and 42.7%, 46.0%, and 11.3% for coronary disease patients (p = 0.02), respectively. Smoking, dyslipidemia, family history, and lipoprotein(a) and lymphotoxin-alfa mutations in men were independent variables associated with coronary disease. The area under the curve (C-statistic) increased from 0.779 to 0.802 (p<0.05) with the inclusion of lipoprotein(a) and lymphotoxin-alfa mutations in the set of conventional risk factors.

CONCLUSIONS:

The inclusion of lipoprotein(a) and lymphotoxin-alfa mutations in the set of conventional risk factors showed an additive but small increase in the risk prediction of premature coronary disease.     

Association of eNOS (G894T,rs1799983) and KCNJ11 (E23K,rs5219) gene polymorphism with coronary artery disease in North Indian population

BackgroundEndothelial nitric oxide synthase (eNOS) and potassium voltage-gated channel subfamily J member 11 (KCNJ11) could be the candidate genes for coronary artery disease (CAD). This study investigated the relationship of the eNOS (rs1799983) and KCNJ11 (rs5219) polymorphisms with the presence and severity of CAD in the North Indian population.MethodsThis study included 300 subjects, 150 CAD cases and 150 healthy controls. Single nucleotide polymorphism was evaluated by Polymerase chain reaction and Restriction fragment length polymorphism (PCR-RFLP). Analysis was performed by SPSS (version 21.0).ResultsWe observed that KK genotype of KCNJ11E23K (rs5219) polymorphism (P=0.0001) genotypes and K allele (P=0.0001) was found to be a positive risk factor and strongly associated with CAD. In the case of eNOSG894T (rs1799983) there was no association found with CAD.ConclusionThese results illustrate the probability of associations between SNPs and CAD although specific genetic polymorphisms affecting ion channel function and expression have still to be clarified by further investigations involving larger cohorts.     

Genetic variants of the class A scavenger receptor gene are associated with coronary artery disease in Chinese

The class A scavenger receptor,encoded by the macrophage scavenger receptor 1(MSR1) gene,is a pattern recognition receptor(PPR) primarily expressed in macrophages.It has been reported that genetic polymorphisms of MSR1 are significantly associated with the number of diseased vessels and coronary artery narrowing greater than 20% in Caucasians.However,whether it links genetically to coronary artery disease(CAD) in Chinese is not defined.Here,we performed an independent case-control study in a Chinese population consisting of 402 CAD cases and 400 controls by genotyping ten single nucleotide polymorphisms(SNPs) of MSR1.We found that rs416748 and rs13306541 were significantly associated with an increased risk of CAD with per allele odds ratio(OR) of 1.56 [95% confidence interval(CI) = 1.28-1.90;P < 0.001] and 1.70(95% CI = 1.27-2.27;P < 0.001),respectively.Our results indicate that genetic variants of MSR1 may serve as predictive markers for the risk of CAD in combination with traditional risk factors of CAD in Chinese population.