Proinflammatory and anti-inflammatory cytokines in pregnant women chronically infected with Trypanosoma cruzi

Mother-to-child transmission of intracellular parasites could be related to the production of immunoregulatory cytokines. The levels of gamma interferon (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and lnterleukin (IL)-10 were evaluated during pregnancy in sera of women chronically infected with Trypanosoma cruzi that delivered infected or non-infected children. The levels of IL-10 increased in both, women only pregnant and only infected, compared to non-infected non-pregnant women. However, in pregnant women chronically infected with T. cruzi, IL-10 did not increase significantly, neither in the mothers of infected nor in the mothers of non-infected children. The levels of the inflammatory cytokine TNF-alpha were not affected in normal pregnancy but increased in the infected mothers of non-infected children. The levels of IFN-gamma did not increase in the groups studied, indicating that the production of this pro-inflammatory cytokine was controlled, even when the levels of IL-10 did not increase, as in pregnant women chronically infected with T. cruzi.     

Serum concentrations of nitric oxide, tumor necrosis factor (TNF)-alpha and TNF soluble receptors in women with overweight and obesity

The aims of the present study was to examine how overweight and obesity affect serum concentrations nitric oxide (NO) metabolites and to determine whether there is association between serum concentrations tumor necrosis factor (TNF)-alpha and TNF soluble receptors (sTNF-R) in subjects with overweight and obesity. The study groups involved 154 women: 102 obese (81 obese with body mass index [BMI] 30 to 40 kg/m2 and 21 obese with BMI > 40 kg/m2), 24 overweight patients, and 28 lean controls. Serum concentrations of NO metabolites and of TNF-alpha and its soluble receptors (sTNF-R1, sTNFR-2) were measured by enzyme-linked immunosorbent assay (ELISA) kits. Serum concentration of insulin was measured by radioimmunoassay (RIA). Plasma glucose, cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglicerydes were determined by enzymatic procedure. Body composition was determined by impedance analysis using Bodystat (Douglas, British Isles). Serum concentrations of NO in the overweight group (35.1 +/- 12.1 micromol/L) and the obese groups with BMI 30 to 40 kg/m2 (32.8 +/- 9.3 micromol/L) and with BMI greater than 40 kg/m2 (33.3 +/- 8.5 micromol/L) were significantly higher when compared to controls (28.2 +/- 8.1 micromol/L): P < .05; P < .01, and P < .01, respectively. There was no difference in levels of NO between the overweight group and both obese groups. Serum concentration of TNF-alpha was also significantly higher in the group with overweight (6.5 +/- 3.1 pg/mL), in the obese group with BMI 30 to 40 kg/m2 (6.8 +/- 3.1 pg/mL), and in the obese group with BMI greater than 40 kg/m2 (7.4 +/- 2.6 pg/mL) when compared to controls (2.9 +/- 2.2 pg/mL): P < .00005; P < .00005, and P < .0000001, respectively. However, serum concentrations of sTNF-R1 and -R2 did not differ significantly between the overweight group, both obese groups, and controls. In conclusion, we observed increased serum concentrations of TNF-alpha and NO in overweight and obese women. It seems that there is an association between serum concentrations of TNF-alpha and NO; however, this relationship depends on the degree of obesity.     

Serum-soluble tumor necrosis factor receptor 2 (sTNF-R2) level determines clinical outcome in patients with aggressive non-Hodgkin's lymphoma

BACKGROUND: Recently investigators have worked to identify prognostic factors in non-Hodgkin's lymphoma (NHL) so an appropriate therapeutic plan can be put in action. The aim of the present study was to assess the prognostic significance of serum soluble tumor necrosis factor receptor (sTNF-R) 2 in aggressive NHL. METHODS: One hundred and ten consecutive patients with aggressive NHL who were previously untreated (diffuse large B-cell lymphoma; 94, peripheral T-cell lymphoma; 16) were prospectively enrolled in this study between 1997 and 2002. The patients were treated with 6-8 cycles of CHOP or THP-COP regimens. RESULTS: High serum sTNF-Rs level was associated with some poor prognostic factors and low complete remission rate. Patients with high sTNF-R1 (4 ng/mL and over) and sTNF-R2 (15 ng/mL and over) at onset had significantly lower survival rates (5 yr: 19%, 19%) than those with low sTNF-R1 (under 4 ng/mL) and sTNF-R2 (under 15 ng/mL) (62% and 69%), respectively (P < 0.0005 and 0.0001). Multivariate analysis employing sTNF-R2 and some conventional prognostic factors demonstrated that a combination of sTNF-R2 and performance status, and that of sTNF-R2, sIL-2R, and LDH were significant prognostic factors for poor overall survival and for poor event-free survival, respectively. In addition, we attempted to use sTNF-R2 in combination with the international prognostic index (IPI). The patients in the high risk group and those with high sTNF-R2 in the low-intermediate (LI)/high-intermediate (HI) risk group had significantly lower survival rates than the patients in the low risk group and those with low sTNF-R2 in LI/HI risk group (P < 0.0001). CONCLUSIONS: The results suggest that a high serum sTNF-R2 level predicts a poor prognosis in aggressive NHL and may be a useful biomarker for selecting appropriate treatment when used in combination with the IPI.     

Soluble tumor necrosis factor receptors in human inflammatory synovial fluids

Objective. To test synovial fluid (SF) for the presence of soluble fragments originating from distinct tumor necrosis factor receptors (TNF-sR55 and TNF-sR75) which bind to TNF and inhibit its biologic activity. Methods. TNF-sR55 and TNF-sR75 were measured in 62 SF samples by specific immunoassays using monoclonal antibodies. Results. Both TNF-sR were present in all of the SF tested. Their concentrations were higher in SF from patients with seropositive rheumatoid arthritis than in patients with other inflammatory arthritides. The relative amount of TNF-sR75, as compared with TNF-sR55, was higher in seropositive RA SF than in other SF. Conclusion. The balance between TNF and its specific inhibitors may be critical to the biologic outcome mediated by this cytokine.     

Influence of pregnancy on Trypanosoma cruzi parasitemia in chronically infected women in a rural Bolivian community

To determine the role of pregnancy on Trypanosoma cruzi parasitemia, a matched cohort study was carried out in a rural Bolivian community comparing parasite rates in gravidae, puerperae, and non-pregnant infected women. A selection of 67 chronically infected women, who delivered between March 2004 and May 2005, were initially evaluated during the third trimester of pregnancy and again after delivery. They were matched for age, parity, and location with 104 seropositive non-pregnant women, who likewise had submitted blood for microscopic examination for T. cruzi parasites in June 2005. Seroreactive pregnant women had a higher rate of T. cruzi parasitemia (14.9%) than matched non-pregnant infected women (2.9%; P = 0.004). After delivery, parasitemia significantly decreased during puerperium (1.5%) compared with the period of pregnancy (14.9%; P = 0.03). This study showed an increase of parasite loads in maternal peripheral blood, during the third trimester, and a significant decline after delivery.     

Soluble tumor necrosis factor receptors correlate with parasitemia and disease severity in human malaria.

Elevated serum or plasma concentration of immunoreactive tumor necrosis factor (TNF) is consistently detected in patients with malaria. TNF levels correlate with high parasitemia and clinical severity but not always with outcome. Since the effects of TNF may be neutralized by soluble TNF receptors, sera of 30 nonimmune patients with malaria were analyzed before and during antimalarial therapy. High concentrations of receptors R1 (55 kDa) and R2 (75 kDa) were detected immunologically in all sera of untreated patients. Levels of immunoreactive TNF correlated closely with levels of soluble TNF R1 and R2 (r = .75 and .59, respectively). In contrast, sera lacked cytotoxic activity against target cells in the TNF bioassays. Soluble TNF receptor levels remained elevated for days after treatment. These results suggest that excessive release of TNF induced by the asexual stage of malaria parasites is controlled by a subsequent shedding of soluble TNF receptors that may bind and deactivate biologically functional TNF.     

Involvement of tumor necrosis factor (TNF) receptors p55 and p75 in TNF responses of acute myeloid leukemia blasts in vitro.

Tumor necrosis factor (TNF)-alpha and TNF-beta have multiple effects on human acute myeloid leukemia (AML) cells in vitro, including (1) synergistic stimulation of proliferation with interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) and upregulation of interleukin-3 (IL-3) and GM-CSF receptors; (2) inhibition of granulocyte-CSF (G-CSF)-induced growth and rapid downmodulation of G-CSF receptors; and (3) induction of autocrine growth. Recently, two distinct TNF receptors (TNF-Rs), TNF-R(p55) and TNF-R(p75), have been identified. In this study, we show that both receptor types may be expressed by AML blasts. It has been investigated whether the different effects of TNF on AML blasts can be explained by differential activation of the distinct TNF-R structures. For this purpose, we used the monoclonal antibodies HTR-1 and HTR-9, specifically recognizing TNF-R(p55), and UTR-1, specific for TNF-R(p75). TNF-(alpha and -beta) mediated synergistic activation with IL-3/GM-CSF, upregulation of IL-3/GM-CSF receptors, inhibition of G-CSF-induced growth, and rapid downmodulation of G-CSF receptors exclusively result from activation of TNF-R(p55). In certain cases in which TNF-alpha, rather than TNF-beta, induces AML growth through an autocrine mechanism, both TNF-R(p55) and (p75) are involved. These data indicate that the variety of TNF responses observed in AML can only be partially explained by differential activation of the TNF-R(p55) and (p75) structures, and that TNF-R(p55) on AML blasts can transduce both positive (synergism with IL-3/GM-CSF) and negative regulatory signals (inhibition of G-CSF-induced proliferation) following TNF activation.     

Tumor necrosis factor (TNF) receptor-1 (TNFp55) signal transduction and macrophage-derived soluble TNF are crucial for nitric oxide-mediated Trypanosoma congolense parasite killing

Control of Trypanosoma congolense infections requires an early cell-mediated immune response. To unravel the role of tumor necrosis factor (TNF) in this process, 6 different T. congolense strains were used in 6 different gene-deficient mouse models that included TNF(-/-), TNF receptor-1 (TNFp55)(-/-), and TNF receptor-2 (TNFp75)(-/-) mice, 2 cell type-specific TNF(-/-) mice, as well as TNF-knock-in mice that expressed only membrane-bound TNF. Our results indicate that soluble TNF produced by macrophages/neutrophils and TNFp55 signaling are essential and sufficient to control parasitemia. The downstream mechanism in the control of T. congolense infection depends on inducible nitric oxide synthase activation in the liver. Such a role for nitric oxide is corroborated ex vivo, because the inhibitor N(G)-monomethyl-l-arginine blocks the trypanolytic activity of the adherent liver cell population, whereas exogenous interferon- gamma that stimulates nitric oxide production enhances parasite killing. In conclusion, the control of T. congolense infection depends on macrophage/neutrophil-derived soluble TNF and intact TNFp55 signaling, which induces trypanolytic nitric oxide.     

Regulation of tumour necrosis factor (TNF) induced apoptosis by soluble TNF receptors in Helicobacter pylori infection

BACKGROUND: Tumour necrosis factor (TNF) is a predominant cytokine produced in the gastric mucosa of patients with Helicobacter pylori infection. TNF induces apoptosis in a variety of cells. The soluble TNF receptors (sTNF-Rs) can be divided into sTNF-RI and sTNF-RII, both of which inhibit TNF activity. However, their precise mechanisms remain unclear. AIM: To investigate the role of sTNF-Rs in H pylori infection. METHODS: In 40 patients, production of TNF and sTNF-Rs in gastric mucosa was measured using biopsy specimens. In addition, in gastric epithelial cells, sTNF-R release in response to TNF and the protective effect of sTNF-Rs against the cytotoxic and apoptotic activities of TNF were examined. RESULTS: TNF and sTNF-R expression was significantly higher in H pylori positive than H pylori negative patients. TNF dose-dependently induced sTNF-RI release from gastric epithelial cells. sTNF-RII was also released from the cells. TNF decreased cell viability, but the effect was very small. A combination of anti-sTNF-RI and anti-sTNF-RII monoclonal antibodies significantly increased TNF induced cytotoxicity and apoptosis of gastric epithelial cells. CONCLUSIONS: These results show that sTNF-Rs are actively produced in H pylori infected gastric mucosa. sTNF-Rs appear to protect gastric epithelial cells from TNF induced apoptosis in H pylori infection.     

Plasma concentrations of tumor necrosis factor-alpha (TNF-alpha) and soluble TNF receptors in patients with anorexia nervosa

Tumor necrosis factor-alpha (TNF-alpha) is a cytokine with numerous immunological and metabolic activities. To study the role of TNF-alpha on the pathophysiology of anorexia nervosa and its complications, plasma concentrations of TNF-alpha, 2 soluble TNF receptors (sTNF-RI and sTNF-RII), and leptin were measured in 20 female patients with anorexia nervosa (AN) and 20 age-matched normal women (N). Plasma TNF-alpha concentrations in AN were significantly higher than those in N (4.1 +/- 0.6 pg/mL vs. 1.6 +/- 0.1 pg/mL; P < 0.01). Although no significant difference was observed in plasma sTNF-RI concentrations between the two groups, plasma sTNF-RII concentrations in AN were significantly higher than those in N (2094.0 +/- 138.5 pg/mL vs. 1569.5 +/- 84.0 pg/mL; P < 0.01). Plasma concentrations of TNF-alpha and sTNF-RII after treatment of 8 anorectic patients were not different from those before treatment, although body fat mass and plasma leptin concentrations significantly increased after treatment. Plasma TNF-alpha concentrations were not related to body fat mass in anorectic patients. These results suggest that the adipose tissue may not be the immediate source of TNF-alpha in anorectic patients and that TNF-alpha may contribute to the pathophysiology of immunological and metabolic abnormalities in anorexia nervosa.     

Plasma concentrations of tumor necrosis factor-alpha (TNF-alpha) and soluble TNF receptors in patients with bulimia nervosa

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a cytokine with numerous immunological and metabolic activities. In addition, TNF-alpha can stimulate a variety of physiological, neuroendocrine and behavioural responses of the central nervous system. In experimental animals, TNF-alpha induces changes in physiological and behavioural parameters which have also been observed in eating disorders. The biological activities of TNF-alpha are mediated by two structurally related, but functionally distinct receptors, TNF-RI and TNF-RII. Since injection of TNF-alpha results in increased shedding of TNF-alpha receptors, it is likely that TNF-alpha release is reflected by soluble TNF-receptors (sTNF-Rs) levels. AIMS: We studied plasma concentrations of TNF-alpha and two sTNF-Rs (sTNF-RI and sTNF-RII) in female patients with bulimia nervosa. DESIGN AND PATIENTS: Twenty female patients with bulimia nervosa (BN) and 20 age-matched normal women (N) were studied. MEASUREMENTS: Plasma TNF-alpha concentrations were measured by enzyme immunoassay kit and plasma concentrations of sTNF-RI and sTNF-RII were measured by enzyme-linked immunosorbent assay. RESULTS: Plasma TNF-alpha concentrations in BN were significantly higher than those in N (4.7+/- 0.5 ng/l vs. 1.6+/-0.1 ng/l; P<0.01). Although no significant difference was observed in plasma sTNF-RI concentrations between the two groups, plasma sTNF-RII concentrations in BN were significantly higher than those in N (2080.0+/-107.5 ng/l vs. 1569.5 +/-84.0 ng/l; P<0.01). Plasma TNF-alpha concentrations were significantly related to plasma sTNF-RI concentrations (r = 0.511, P<0.05) and to plasma sTNF-RII concentrations (r = 0.532, P<0.05) in bulimic patients. However, plasma TNF-alpha concentrations were not related to body fat mass or to bulimic behaviours in these patients. CONCLUSIONS: Our present findings suggest that the adipose tissue may not be the immediate source of TNF-alpha in bulimic patients but the increase in plasma TNF-alpha in these patients may be derived from the central nervous system sources. The elevated sTNF-RII may reflect different shedding kinetics compared with sTNF-RI in bulimic patients.     

Human macrophage tumor necrosis factor (TNF)-alpha production induced by Trypanosoma brucei gambiense and the role of TNF-alpha in parasite control

Trypanosoma brucei gambiense, a causative agent of sleeping sickness, induced a dose-dependent production of tumor necrosis factor (TNF)-alpha by human macrophages in vitro. TNF-alpha was also induced in the Mono Mac 6 cell line, which indicates a direct effect of parasite components on macrophages. Parasite-soluble factors were also potent inducers of TNF-alpha. The addition of anti-TNF-alpha to cocultures of macrophages and parasites increased the number of trypanosomes and their life span, whereas irrelevant antibodies had no effect. TNF-alpha may have a direct role (i.e., direct trypanolytic activity) and/or an indirect one, such as TNF-alpha-mediated induction of cytotoxic molecules. A direct dose-dependent lytic effect of TNF-alpha on purified parasites was observed. This lytic effect was inhibited by anti-TNF-alpha. These data suggest that, as in experimental trypanosomiasis, TNF-alpha is involved in parasite growth control in human African trypanosomiasis.     

急性病毒性心肌炎患者可溶性白细胞介素-2受体和肿瘤坏死因子

目的 :了解病毒性心肌炎 (VM)患者血清可溶性白细胞介素 - 2受体 (s IL- 2 R)和肿瘤坏死因子 (TNF)的改变 ,并探讨其发病机制。方法 :检测 30例 VM患者血清 s IL- 2 R和 TNF水平及与临床关系。结果 :VM患者血清 s IL- 2 R和 TNF水平明显增高。VM患者中 s IL- 2 R水平高者 ,临床病情亦较重。结论 :s IL- 2 R和 TNF在 VM发病机制中可能起作用 ,其血清学检测有助于临床病情分析。     

Soluble human p55 and p75 tumor necrosis factor receptors reverse spontaneous arthritis in transgenic mice expressing transmembrane tumor necrosis factor alpha

OBJECTIVE: The roles of the transmembrane and secreted forms of tumor necrosis factor alpha (TNFalpha) in rheumatoid arthritis (RA) remain unclear. Agents used to inhibit TNFalpha have shown varying efficacy in RA patients, suggesting that anti-TNFalpha agents possess dissimilar mechanisms of action, including the ability to neutralize transmembrane (tmTNFalpha) and secreted TNFalpha. In this study, TNFalpha-knockout (TNFalpha-KO) mice that were genetically altered to express elevated levels of tmTNFalpha were constructed to further understand the roles of the 17-kd secreted, trimeric, and 26-kd transmembrane forms of TNFalpha. METHODS: A speed-congenic mating scheme was used to generate 3 unique strains of mice: 1) transgenic tmTgA86 mice overexpressing 26-kd tmTNFalpha and also secreting 17-kd trimeric TNFalpha (tmTNFalpha-transgenic), 2) TNFalpha-/- mice (TNFalpha-KO), and 3) transgenic mice overexpressing tmTNFalpha backcrossed to TNFalpha-KO mice (tmTNFalpha-transgenic/TNFalpha-KO). Mice were treated with phosphate buffered saline (as vehicle control), dexamethasone (as positive control), or modified recombinant human soluble TNF receptor (sTNFR) p55 or p75, and were assessed clinically and histopathologically for signs of inflammation and development of arthritis. RESULTS: The tmTNFalpha-transgenic/TNFalpha-KO mice were born with crinkled tails and spinal deformities similar to those in ankylosing spondylitis. By 2-4 weeks, these mice developed symmetric inflammatory arthritis, characterized by tissue swelling, pannus formation, and bone deformities. The tmTNFalpha-transgenic mice also developed spontaneous-onset arthritis, but at a slower rate (100% incidence by 10-12 weeks). Clinical and histologic progression of arthritis in the tmTNFalpha-transgenic/TNFalpha-KO mice was reduced by treatment with dexamethasone or with the p55 or p75 sTNFR (69% and 63% reduction in total histologic score, respectively). CONCLUSION: These data show that arthritis is sufficiently initiated and maintained in tmTNFalpha-transgenic/TNFalpha-KO mice, and that it can be neutralized by recombinant human p55 or p75 sTNFR, resulting in amelioration of the biologic and subsequent histologic destructive effects of tmTNFalpha.     

Soluble human p55 and p75 tumor necrosis factor receptors reverse spontaneous arthritis in transgenic mice expressing transmembrane tumor necrosis factor α

Objective

The roles of the transmembrane and secreted forms of tumor necrosis factor α (TNFα) in rheumatoid arthritis (RA) remain unclear. Agents used to inhibit TNFα have shown varying efficacy in RA patients, suggesting that anti‐TNFα agents possess dissimilar mechanisms of action, including the ability to neutralize transmembrane (tmTNFα) and secreted TNFα. In this study, TNFα‐knockout (TNFα‐KO) mice that were genetically altered to express elevated levels of tmTNFα were constructed to further understand the roles of the 17‐kd secreted, trimeric, and 26‐kd transmembrane forms of TNFα.

Methods

A speed‐congenic mating scheme was used to generate 3 unique strains of mice: 1) transgenic tmTgA86 mice overexpressing 26‐kd tmTNFα and also secreting 17‐kd trimeric TNFα (tmTNFα‐transgenic), 2) TNFα^−/− mice (TNFα‐KO), and 3) transgenic mice overexpressing tmTNFα backcrossed to TNFα‐KO mice (tmTNFα‐transgenic/TNFα‐KO). Mice were treated with phosphate buffered saline (as vehicle control), dexamethasone (as positive control), or modified recombinant human soluble TNF receptor (sTNFR) p55 or p75, and were assessed clinically and histopathologically for signs of inflammation and development of arthritis.

Results

The tmTNFα‐transgenic/TNFα‐KO mice were born with crinkled tails and spinal deformities similar to those in ankylosing spondylitis. By 2–4 weeks, these mice developed symmetric inflammatory arthritis, characterized by tissue swelling, pannus formation, and bone deformities. The tmTNFα‐transgenic mice also developed spontaneous‐onset arthritis, but at a slower rate (100% incidence by 10–12 weeks). Clinical and histologic progression of arthritis in the tmTNFα‐transgenic/TNFα‐KO mice was reduced by treatment with dexamethasone or with the p55 or p75 sTNFR (69% and 63% reduction in total histologic score, respectively).

Conclusion

These data show that arthritis is sufficiently initiated and maintained in tmTNFα‐transgenic/TNFα‐KO mice, and that it can be neutralized by recombinant human p55 or p75 sTNFR, resulting in amelioration of the biologic and subsequent histologic destructive effects of tmTNFα.

     

Soluble tumor necrosis factor receptors in chronic hepatitis C: a correlation with histological fibrosis and activity

BACKGROUND/AIMS: Tumor necrosis factor-alpha (TNF) is a mediator of inflammation and cellular immune response. Soluble TNF receptors (sTNFR) sTNF-R55 and sTNF-R75, which compete with cellular receptors for the binding of TNF, have been detected at high levels in infectious diseases including human immunodeficiency virus and HBV infection. In order to investigate the activation of the TNF system in HCV infection, we have analyzed the balance between TNF and sTNF-R in 60 HCV-infected subjects according to their clinical, biological, virological and histological characteristics. METHODS: Serum TNF, sTNF-R55 and sTNF-R75 levels were determined by ELISA before any therapy and were compared to a control group of 60 healthy subjects and a group of 34 HBV-infected patients. RESULTS: Mean TNF levels were 50.5+/-4.5 pg/ml in HCV patients, and undetectable (<5 pg/ml) in the control subjects. sTNF-R55 and sTNF-R75 levels were significantly higher in HCV-infected patients than in the controls: 2.88+/-0.14 ng/ml vs. 1.30+/-0.05, (p = 0.0001), and 9.54+/-0.58 ng/ml vs. 4.19+/-016, (p = 0.0001), respectively. sTNF-R55 and TNF-alpha levels in HCV patients were not significantly different from levels in HBV patients. sTNF-R75 levels were slightly lower than in HBV patients (9.54+/-0.58 vs. 11.4+/-0.79 ng/ml, p = 0.03). In contrast to other infectious diseases, there was no correlation between levels of sTNF-R and TNF. sTNF-R75 but not TNF levels were correlated with aminotransferases levels (p = 0.0001 and p = 0.0015 for aspartate and alanine aminotransferase, respectively), while sTNF-R55 levels were significantly correlated only with aspartate aminotransferase levels (p = 0.003). sTNF-R75 levels were significantly correlated with the Metavir activity index (p = 0.01), and sTNF-R55 and sTNF-R75 levels were significantly higher in patients with vs. without cirrhosis (3.22+/-0.21 vs. 2.54+/-0.17 ng/ml (p<0.02) and 11.6+/-0.86 vs. 7.5+/-0.53 ng/ml (p<0.001), respectively). sTNF-R55, sTNF-R75 and TNF levels were not correlated with viral load, genotype or response to interferon therapy. CONCLUSIONS: Levels of soluble TNF receptors, and particularly sTNF-R75, are significantly correlated with the severity of the disease but not with virological parameters such as quantitative viremia and genotype. High TNF-R production could thus suggest that HCV-related liver disease involves immunological mechanisms, including activation of the TNF system.     

内皮素-1基因TaqⅠ和肿瘤坏死因子α基因多态性与肝硬化门静脉高压的相关性

目的 探讨内皮素-1基因Taq Ⅰ多态性和肿瘤坏死因子(TNF)α基因多态性与肝硬化门静脉高压之间的相互关系。 方法 采用病例对照和聚合酶链反应-限制性片段长度多态性等技术,检测了106例乙型肝炎后肝硬化患者和108名健康对照者内皮素～1基因Taq Ⅰ多态性和TNF α基因启动子-308G→A多态性,比较等位基因及基因型频率,并进行分层分析。 结果 在ET—1基因Taq Ⅰ多态性中,门静脉高压症组(LC )C等位基因频率和CC TC基因型频率分别为25.38％与46.15％,比正常对照组明显升高(16.67％与30.56％,x2=4.26,P<0.05)。在TNF α基因多态性中,LC 组TNF2/1基因型的频率比对照组明显升高(21.54％对10.19％,P<0.05)。分层分析发现由这两个基因多态性组成的不同基因型中,TCF 2基因型频率在LC 组高于正常对照组(P<0.05,OR=2.03)。Logistic多元逻辐回归分析显示,ET-1和TNFα基因多态性是门静脉高压形成的危险因子(P值分别为0.022和0.043)。 结论 ET—1和TNF α基因多态性与肝硬化门静脉高压症相关,是门静脉高压症形成的新的危险因子。TCF2基因型可能是门静脉高压症的易感基因型。