类风湿关节炎患者血清sTNF—R、TNF—α的变化

目的为探讨类风湿关节炎 (RA)与可溶性肿瘤坏死因子受体 (s TNF- R)、TNF- α、TNF- α/ s TNF- R比值的关系。方法应用双抗体夹心 EL ISA法检测了活动期 RA(2 8例 ) ,稳定期 RA (12例 )及健康人 (30例 )血清中 s TNF- R 、s TNF- R 、TNF-α的水平。结果活动期 RA患者血清 s TNF- R 、s TNF- R 、TNF-α水平明显高于健康人及稳定期 RA组 ,P均 <0 .0 1。稳定期 RA患者血清 s TNF- R 、s TNF- R 、TNF-α水平亦明显高于健康人 ,P<0 .0 1。在 RA患者中 ,血清 s TNF- R 、s TNF- R 水平与 ESR、CRP、Ritchie index呈显著正相关 ,与类风湿因子 (RF)水平无相关性。RA患者治疗 3个月后 s TNF- R 、s TNF- R 及 TNF- α/ s TNF R比值显著下降。结论 RA患者血清 s TNF- R 、s TNFR- 水平显著增高 ,且与疾病活动度呈正相关。测定血清 s TNF- R 、s TNF- R 、TNF- α/ s TNF- R水平可作为 RA诊断 ,监测疾病活动、治疗及判断预后的一项有意义的实验室指标     

Elevated serum levels of soluble tumour necrosis factor receptors (sTNF-R) in patients with HIV infection.

Serum levels of the soluble form of tumour necrosis factor receptor type II (p75) (sTNF-R) were determined in HIV-infected individuals and risk groups and were then correlated with the course of infection and prognosis. sTNF-R levels were determined by an ELISA with MoAbs and polyclonal antibodies to urine-derived sTNF-R proteins. The mean +/- s.e. levels of sTNF-R in the sera of 49 HIV+ male homosexuals, 34 HIV- male homosexuals and 44 matched controls were 6.1 +/- 0.3 ng/ml, 4.4 +/- 0.3 ng/ml and 3.4 +/- 0.2 ng/ml, respectively. All these values were significantly different between each of the groups (P less than 0.001-0.05). Sequential studies of sTNF-R revealed higher levels following seroconversion in 5/8 individuals, remained persistently high during the asymptomatic phase of the infection and became even more elevated in some ARC and AIDS patients. At the same time TNF-alpha was undetectable in sera obtained from HIV+ male homosexuals and from healthy controls. This was independent of stage of HIV infection, serum sTNF-R level and type of ELISA kit used. These findings suggest that TNF-alpha/TNF-R system is turned on before and during HIV infection and raise the possibility that sTNF-R, the natural inhibitor of TNF, may be of importance in determining the course and probably prognosis of the disease.     

Control of established experimental allergic encephalomyelitis by inhibition of tumor necrosis factor (TNF) activity within the central nervous system using monoclonal antibodies and TNF receptor-immunoglobulin fusion proteins

Tumor necrosis factor (TNF) activity was inhibited during the development of actively-induced, chronic relapsing experimental allergic encephalomyelitis (CREAE) in Biozzi AB/H mice, using a mouse TNF-specific (TN3.19.12) antibody and bivalent human p55 and p75 TNF receptor-immunoglobulin (TNFR-Ig) fusion proteins. The development of disease could be inhibited when repeated doses of antibody were administered prior to the anticipated onset. It has now also been shown that a therapeutic effect is evident even when antibody is administered after the onset of clinical signs, further indicating an important role for TNF in pathogenic effector mechanisms in CREAE. Although biologically-active TNF was not detected in the circulation, TNF-α was detected in lesions within the central nervous system (CNS). This suggested that the CNS may be the main site for TNF-specific immunomodulation and was supported by the observation that intracranial injection was significantly more potent than that administered systemically, for both antibody and TNFR-Ig fusion proteins. The fusion proteins were as effective as antibody at doses 10—100-fold lower than that used for antibody, reflecting their higher neutralizing capacity in vitro. Although treatment was not curative and relapse inevitably occurred in this model if treatment was not sustained, the data indicate that anti-TNF immunotherapy, especially within the CNS, can inhibit CREAE and may, therefore, be useful in the control of human neuroimmunological diseases.     

No independent association between a tumor necrosis factor-α promotor region polymorphism and insulin-dependent diabetes mellitus

Several studies have implicated tumor necrosis factor (TNF)-α in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). In the present study we analyzed the first reported TNF-α gene polymorphism in relation to IDDM. We have made frequence analysis and tested in vitro lipopolysaccharide (LPS)-induced TNF-α secretion. A significant difference in allele frequency was observed between patients and controls (p = 0.03). However, a very strong association of the uncommonTNF2 allele was observed with the HLA-B8, –DR3 alleles. The relative risk (RR) of TNF2 was 2.2 compared to a RRof 3.1 for DR3. One reason for this difference was the identification of the TNF1 allele on the otherwise strongly IDDM-associated HLA-DR3 haplotype: DQB1*0201, DQA1*0501, DRB1*0301, TNFc2, TNFB*2, TNFal, TNFb5, B18. Thus, the IDDM-associated TNF2 allele had no DR3-independent value as a disease marker. The LPS-induced TNF-α production by human monocytes in relation to genotypes demonstrated that TNF1/2 heterozygous individuals had higher, though not statistically significantly (p = 0.08) levels than TNF1-homozygous subjects. However, this difference was rather small, unlikely to be of biological significance and based on the present material we cannot establish the functional importance of this polymorphism.     

Two inhibitors of pro-inflammatory cytokine release,interleukin-10 and interleukin-4, have contrasting effects on release of soluble p75 tumor necrosis factor receptor by cultured monocytes

The biological activity of the pro-inflammatory cytokine, tumor necrosis factor (TNF)-α depends on the level of TNF-α itself, the expression of the p55 and p75 cell surface receptors for TNF on target cells and the concentrations of the natural inhibitors of TNF-α, the soluble p55 and p75 TNF receptors (TNF-R). Interleukin (IL)-10 and IL-4 are known to inhibit TNF-α production by monocytes. We, therefore, investigated the effects of IL-10 and IL-4 on the cell surface expression and release of TNF-R by human monocytes to determine whether these cytokines also indirectly modulated the biological activity of TNF-α. Exposure to IL-10 (1-10 U/ml) for 24 or 48 h increased soluble p75 TNF-R expression and concomitantly reduced surface expression of p75 TNF-R. Further, IL-l α-stimulated production of TNF-α was diminished by IL-10 and only a small proportion of this TNF-α was bioactive, consistent with increased production of inhibitory soluble TNF-R. IL-10 also induced down-regulation of surface p55 TNF-R on monocytes, and increased release of soluble p55 TNF-R. However, the expression of soluble p55 TNF-R was much lower than soluble p75 TNF-R, indicating that it contributed less importantly to neutralization of TNF-α under these conditions. Like IL-10, IL-4 supressed the release of TNF-α by monocytes. In contrast to IL-10, however, IL-4 (0.1-10 ng/ml) supressed the release of soluble p75 TNF-R from monocytes in a dose-dependent manner. Release of soluble p55 TNF-R was also supressed by IL-4. IL-10, therefore, reduces the pro-inflammatory potential of TNF in three ways: by down-regulating surface TNF-R expression whilst increasing production of soluble TNF-R and inhibiting the release of TNF-α itself. This suggests that IL-10 may be useful in the treatment of diseases where overexpression of TNF-α occurs.     

Tumour necrosis factor (TNF) gene polymorphism influences TNF-α production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans

TNF-α is involved in infectious and immuno-inflammatory diseases. Different individuals may have different capacities for TNF-α production. This might determine a predisposition to develop some complications or phenotypes of these diseases. The aims of our study were to assess the inter-individual variability of TNF-α production and to correlate this variability to a single base pair polymorphism located at position ?308 in TNF gene. We studied 62 healthy individuals. TNF-α production after LPS stimulation was evaluated using a whole blood cell culture model. The TNF gene polymorphism was studied by an allele-specific polymerase chain reaction. Other cytokines produced in the culture, soluble CD14 concentrations and expression of CD14 on blood cells were also measured. Among the 62 individuals, 57 were successfully genotyped. There were 41 TNF1 homozygotes and 16 TNF1/TNF2 heterozygotes. TNF-α production after LPS stimulation of whole blood cell culture was higher among TNF2 carriers than among TNF1 homozygotes (929 pg/ml (480–1473 pg/ml) versus 521 pg/ml (178–1307 pg/ml); P < 0.05). This difference was even more significant after correction of TNF-α production for CD14 expression on blood cells. In conclusion, the single base pair polymorphism at position ?308 in the TNF gene may influence TNF-α production in healthy individuals.     

Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF-a and TNF-0 by human mononuclear cells: a possible link to insulin-dependent diabetes mellitus

We have investigated the correlation between different tumor necrosis factor (TNF) and class II major histocompatibility complex alleles in the lipopolysaccharide- or phytohemagglutinin-induced secretion of TNF-α and TNF-β by human monocytes and peripheral blood mononuclear cells in 87 unrelated Danish male individuals. Significant differences in TNF-α secretory capacity between TNF Ncol restriction fragment length polymorphisms, TNFa and TNFc micro-satellite alleles and DR alleles were identified. No correlation with TNF-β secretory capacity was found for any of the markers studied. TNF genotyping allowed us to define four extended HLA haplotypes which correlate with TNF-α secretory capacity. Two of these are DR4 positive: DQw8, DR4, TNFB*1, TNFa6, B44, A2 and DQw8, DR4, TNFB*2, TNFa2, B15, A2. Individuals carrying the TNFB*2, TNFa2 haplotype had a higher TNF-α secretory capacity than those carrying the TNFB*1, TNFa6 haplotype. In a group of DR3/DR4 heterozygous patients with insulin-dependent diabetes mellitus (IDDM), the frequency of the TNFa2 allele was higher than in HLA-DR matched controls, whereas theTNFa6 allele was more frequent in control individuals. In the DR3/DR4 heterozygous diabetic group 12/26 had the alleles combination DQw8, DR4 (Dw4), C4A3, TNFB*2, TNFa2, B15, whereas only 1/18 controls had this haplotype. This diabetogenic haplotype is identical to the DR4 haplotype which correlates with a higher TNF-α response. These observations suggest a direct role for the TNF locus in the pathogenesis of IDDM.     

乳腺癌患者化疗前后血清leptin、TNF-α和STNFR检测的临床意义

目的：探讨乳腺癌患者化疗前后血清瘦素（leptin）、肿瘤坏死因子-α（TNF-α）和可溶性肿瘤坏死因子受体（STNFR）水平的变化及临床意义。方法：应用放射免疫分析和ELISA对33例肺癌患者进行了化疗前后血清leptin、TNF-α和STNFR测定,并与35名正常健康人作比较。结果：在化疗前,乳腺癌患者血清leptin、TNF-α和STNFR水平非常显著地高于正常人组（P〈0.01）,经化疗后3个月与正常人组比较仍有差异（P〈0.05）。结论：检测乳腺癌患者血清leptin、TNF-α和STNFR水平的变化对了解病情、观察疗效和预后均有重要的临床价值。     

Higher serum levels of tumour necrosis factor and its soluble receptors are associated with ovarian tumours

Introduction

Tumour necrosis factor (TNF) and its soluble receptors type 1 (sTNF-R1) and type 2 (sTNF-R2) have been suggested as key mediators between apoptosis and cancer cell progression. The aim was to examine concentrations of the parameters in the serum of women with ovarian tumour and in the fluid from ovarian cysts of women with serous cystadenoma.

Material and methods

The study included 125 women with ovarian tumours. As a control, sera were obtained from 70 healthy female volunteers. Concentrations of TNF, sTNF-R1 and sTNF-R2 were measured by enzyme-linked immunosorbent assay (ELISA).

Results

Significant increases of TNF, sTNF-R1 and sTNF-R2 were found in the serum of women with ovarian tumour in comparison to the control (p < 0.0001). The highest levels of all studied parameters were observed in women with ovarian cancer. In the ovarian cyst fluid the concentrations of the evaluated parameters increased significantly as compared to the serum (p < 0.0001).

Conclusions

Our data showed changes in regulatory mechanisms of apoptosis in women with ovarian tumours which are associated with increased concentrations of all studied factors. Serum estimated TNF and especially sTNF-R may be used as complementary diagnostic markers in patients with ovarian tumours.     

慢性丙型肝炎患者血清TNF-α水平与干扰素-α治疗的关系及影响因素

目的 探讨慢性丙型肝炎(慢丙肝)患者血清肿瘤坏死因子-α(TNF-α)水平与病变程度、病毒学指标、抗病毒治疗应答效果之间的相关性.方法 102例慢丙肝和30例健康对照检测血清TNF-α水平,慢丙肝按肝功实验室检查异常程度分为轻度44例、中度34例、重度24例,慢丙肝进行血肝功能检测、HCV RNA载量、HCV基因型的检测.结果 血清TNF-α水平慢丙肝患者高于健康对照;肝功能异常轻度者低于中度和重度;与CHE呈正相关;与DBIL呈负相关;与HCV RNA载量无相关性;在不同HCV基因型感染者间差异无统计学意义;与干扰素-α治疗疗效无关.结论 慢丙肝患者血清TNF-α水平高于健康对照组,并与病变程度相关,与干扰素-α治疗疗效无关.     

小儿急性肾炎患者治疗前后血清TNF-α和血浆VEGF水平变化的临床意义

目的：探讨了小儿急性肾炎患者治疗前后血清TNF-α和血浆VEGF水平的变化。方法：分别应用放免法和酶联双抗体夹心法测定了32例小儿急性肾炎患者血清TNF-α和VEGF含量,并与35名正常小儿作比较。结果：小儿急性肾炎患者在治疗前血清TNF-α和VEGF水平均非常显著地高于正常人组（P〈0.01）,经中西医结合治疗一个月后与正常人比较仍有差异（P〈0.05）。结论：小儿急性肾炎的发生、发展与血清TNF-α和血浆VEGF水平密切相关。     

Lack of soluble TNF-receptors in women with recurrent spontaneous abortion and possibility for its correction

PROBLEM: Tumor necrosis factor (TNF) and soluble TNF receptors (sTNF-Rs) system related with Th1 and Th2 and activity of NF-kappaB/IkappaB regulatory system. This study was designed to compare sTNF-R1 and sTNF-R2 production (shedding) and levels of late activated CD8+ T-lymphocytes in non-pregnant (n = 30) and pregnant (n = 20) normal women and non-pregnant (n = 20) and pregnant (n = 30) RSA women. Effects of progesterone (natural structure) injections in RSA women were studied. METHODS OF STUDY: Levels of sTNF-R1, sTNF-R2, TNF in peripheral blood serum were detected by enzyme-linked immunosorbent assay. Lymphocyte subsets were estimated by multicolor flow cytometry. NK cell cytotoxic activity of peripheral blood lymphocytes (PBL) in whole blood against K562 targets was determined using Europium-release cytotoxicity assay. Mitogen-induced proliferative response of PBL to PHA-P, Con A and PWM were determined by standard 3H-thymidine incorporation assay. RESULTS: Levels of soluble TNF-R1 and TNF-R2 in normal pregnancy were elevated when compared with non-pregnant normal women and pregnant RSA women. Levels of late activated CD8+ T-lymphocytes in normal pregnancy were decreased but no changes were detected in RSA women. After progesterone therapy (i.m. injections of 2.5% oil solution) in RSA women elevation of sTNF-R1 and sTNF-R2 to normal pregnancy ranges was observed. No changes in levels of late activated CD8+ T-lymphocytes after progesterone treatment were detected. CONCLUSIONS: Elevation of levels of sTNF-R1, sTNF-R2 and decrease of late activated cytotoxic T-lymphocytes are pronounce markers of normal human pregnancy. In RSA women there are no elevation of sTNF-R1 and sTNF-R2 levels during pregnancy. This deficiency may be restored by progesterone treatment.     

Predominant pathogenic role of tumor necrosis factor in experimental colitis in mice

Antibodies to tumor necrosis factor (TNF)-α have been recently proposed as effective treatment for patients with Crohn's disease. Here, we analyze the functional role of TNF-α in a mouse model of chronic intestinal inflammation induced by the hapten reagent 2,4,6,-trinitrobenzene sulfonic acid (TNBS) that mimics some characteristics of Crohn's disease in humans. Macrophage-enriched lamina propria (LP) mononuclear cells from mice with TNBS-induced colitis produced 10–30-fold higher levels of TNF-α mRNA and protein than cells from control mice. When mice with chronic colitis were treated by intraperitoneal injection of antibodies to TNF-α, an improvement of both the clinical and histopathologic signs of disease was found. Isolated macrophage-enriched LP cells from anti-TNF-α-treated mice produced strikingly less pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6 in cell culture. The predominant role of TNF-α in the mouse TNBS-induced colitis model was further underlined by the finding that striking colonic inflammation and lethal pancolitis was induced in TNF-α-transgenic mice upon TNBS treatment. Conversely, no significant TNBS-induced colitis could be induced in mice in which the TNF-α gene had been inactivated by homologous recombination. Complementation of TNF-α function in TNF^?/? mice by the expression of a mouse TNF-α transgene was sufficient to reverse this effect. Taken together, the data provide direct evidence for a predominant role of TNF-α in a mouse model of chronic intestinal inflammation and encourage further clinical trials with antibodies to TNF-α for the treatment of patients with Crohn's disease.     

IgA1与系膜细胞共培养上清对足细胞分泌TNF-α的影响及机制探讨

目的： 探讨IgA肾病血清IgA1与系膜细胞共培养上清对足细胞分泌TNF-α的影响及机制。方法：Jacalin 亲和层析柱和Sephacryl S-200 分子筛用来纯化蛋白,单体IgA1（mIgA1)热聚合为聚合体IgA1(aIgA1), 同步化的系膜细胞与患者和健康对照来源的aIgA1共培养,收集上清,分别与同步化的足细胞作用;ELISA检测足细胞上清TNF-α水平,real time PCR 检测凋亡相关基因Ang、ACE mRNA表达情况。结果：IgAN患者来源的aIgA1与系膜细胞共培养得到上清可刺激足细胞分泌TNF-α,其水平显著高于对照组［(12.47±1.45) ng/L vs (2.33±0.65) ng/L,P<0.05］。与对照和健康上清组相比,该上清可上调足细胞Ang和ACE mRNA显著升高(P<0.05)。依那普利拉(10-5 mol/L)可使该上清作用后的足细胞分泌的TNF-α显著下降至(7.52±1.12) ng/L (P<0.05);而缬沙坦(10-5 mol/L)则使之下降至(6.64±0.68) ng/L (P<0.05);而依那普利拉(0.5×10-5 mol/L)和缬沙坦(0.5×10-5 mol/L)联合治疗可使足细胞TNF-α下降至(2.72±0.55) ng/L,与对照无显著差异(P>0.05)。结论：IgA肾病患者血清IgA1与系膜细胞共培养上清可通过激活肾素-血管紧张素系统而刺激足细胞TNF-α分泌,参与IgAN的进展。     

原发性肾小球疾病患者花生四烯酸和肿瘤坏死因子α的变化

目的: 探讨原发性肾小球疾病患者体内花生四烯酸(AA)和肿瘤坏死因子α(TNF-α)的变化及对氧化应激的影响。方法: 以经临床和肾活检确诊原发性肾小球疾病患者55例为研究对象,按肾小球滤过率(GFR)分为慢性肾脏病(CKD)1、2期,CKD3、4期和CKD5期3个组,用酶联免疫吸附测定试剂盒(ELISA)测患者血清游离AA、TNF-α、丙二醛(MDA)和高敏C反应蛋白(hs-CRP)浓度。结果: CKD1、2期和3、4期患者之间AA和MDA差异无统计学意义(P>0.05),CKD5期AA明显高于其它各组(P<0.05),而MDA明显低于其它各组(P<0.05)。CKD3、4期和5期之间的TNF-α差异无统计学意义(P>0.05),但都明显低于CKD1、2期(P<0.05)。各组间hs-CRP差异无统计学意义(P>0.05)。MDA与AA呈负相关(r=-0.752,P<0.01),与TNF-α呈正相关(r=0.463,P<0.01),MDA(Y)与AA(X₁)和TNF-α(X₂)的多元线性回归方程为 Y=1 361.723-2.661X₁+9.320X₂(F=52.445, P<0.01)。结论: AA和TNF-α是影响原发性肾小球疾病患者氧化应激的重要因素,AA具有抑制氧化应激的作用,TNF-α具有促进氧化应激作用。     

Serum levels of the soluble receptor for tumor necrosis factor in patients with renal disease

Tumor necrosis factor- (TNF-) has been found to be elevated in patients during hemodialysis and is thought to mediate some of the immune and metabolic dysfunctions in these patients. It has been speculated that infusions of soluble TNF receptor (sTNF-R) may prevent some of the cytotoxic effects of TNF. However, little is still known about preexisting serum TNF-R levels in patients with chronic renal failure, with or without hemodialysis. Therefore we analyzed serum samples of sTNF-R in 26 patients with chronic renal failure (group I), 6I hemodialysis patients (group II), 9 renal transplant recipients with acute renal failure requiring posttransplant dialysis (group III), 13 renal transplant patients with rejection and moderate kidney dysfunction (group IV), and 21 renal transplant recipients with borderline kidney dysfunction and diverse infectious complications (group V). Control groups consisted of 34 blood donors and diseased controls (11 renal transplant recipients with normal kidney function without complications). All patient groups showed significantly higher sTNF-R levels compared to the control groups. In groups I, IV, and V comparable levels were observed. In group I there was a clear correlation between sTNF-R levels and serum creatinine. The highest sTNF-R serum levels were seen in groups II and III, but there was no correlation with creatinine. In the posttransplant cases (group III and diseased controls) there was a decrease in sTNF-R with improvement of kidney function. These data strongly suggest that sTNF-R serum levels are dependent on kidney function.Abbreviations TNF tumor necrosis factor - TNF-R tumor necrosis factor receptor - sTNF-R soluble tumor necrosis factor receptor - RTX renal transplantation - ELISA enzyme-linked immunosorbent assay Correspondence to: G. Halwachs     

Tumour necrosis factor-alpha (TNF), lymphotoxin and TNF receptor levels in serum from patients with Wegener's granulomatosis

Wegener's granulomatosis (WG) is a systemic inflammatory disease with vasculitis as the key feature. Abnormal expression of tumour necrosis factor alpha (TNFalpha) is considered of prime pathogenic importance in several inflammatory diseases. The effects of TNFa are mediated by TNF receptors (TNF-R), and these receptors are often found in soluble forms (sTNF-R), which can modulate TNFalpha actions. To evaluate the clinical importance of the TNF family of cytokines, the serum levels of TNFalpha, TNFbeta, now termed lymphotoxin (LTalpha), and sTNF-R1 and sTNF-R2 were measured by ELISA in 8 patients with WG during active disease and during immunosuppressive treatment, and in 11 healthy controls in parallel. Serum concentrations of TNFalpha were undetectable in all except two controls (18%) and three patients with WG (37%). After 7 days of therapy, six of the WG patients had measurable TNFalpha levels. Examination of the relative amounts of TNFalpha and sTNF-R indicated that TNFalpha was mostly bound to its soluble receptors. In WG, the serum levels of sTNF-R1 and sTNF-R2 were dramatically increased (p<0.01), with little or no variation during treatment. While the IL-1beta levels did not deviate significantly from controls, the IL-1ra levels were significantly elevated in the WG patients throughout the study period (p<0.01).     

抗甲状腺药物影响Graves’病患者外周血细胞因子水平的表达

目的：研究抗甲状腺药物对Graves’病（GD）患者血清细胞因子水平的影响。方法：用放射免疫分析检测30例GD患者抗甲状腺药物治疗前后血清白细胞介素-2（IL-2）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）水平,30例年龄与性别相匹配的健康者作为正常对照组。结果：GD患者血清IL-6、TNF-α水平显著高于正常对照组（P〈0.01）,IL-2显著低于正常对照组（P〈0.01）;抗甲状腺药物治疗,甲状腺功能恢复正常后,IL-2明显升高,与正常对照组比较差异无显著性（P〉0.05）;IL-6、TNF-α明显低于治疗前（P〈0.01）,但仍高于正常对照组（P〈0.05）。结论：抗甲状腺药物治疗前后血清细胞因子水平的变化可能与发病机制、治疗效果和预后有关。     

TNF-α基因单核苷酸多态性与肺炎的相关性研究

目的： 以中国南方汉族人群为研究对象，探讨肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)基因启动子区单核苷酸多态性(single-nucleotide polymorphisms,SNPs)与肺炎易感性以及肺炎严重程度的相关性。方法: 以67例肺炎患者和50例健康人群为研究对象，应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对TNF-α基因启动子区5个位点(-1 031、-863、-857、-308、-238)进行基因分型，用SPSS统计软件分析各多态性位点与肺炎严重程度的相关性。结果: TNF-α基因启动子区总突变频率在肺炎患者中高于健康体检者(56.7%，38.0%，P<0.05)，-863A在重症肺炎患者与非重症肺炎患者中出现频率分别为〖JP2〗44.4%与15.5%，P<0.05；-308A在重症肺炎患者与非重症肺炎患者中出现频率分别为44.4%与12.1%，P<0.05，〖JP〗在死亡与存活病例中的频率分别为75.0%与12.7%，P<0.01。结论: TNF-α基因启动子区多态性可能是肺炎易感以及肺炎进展为重症肺炎、增加重症肺炎患者死亡率的因素。