Correlation between neopterin,interferon-gamma and haemoglobin in patients with haematological disorders

Abstract: In this study, we further investigated a possible link between activation of cell-mediated immunity and anaemia in patients with haematological neoplasias. We compared serum concentrations of interferon-gamma and neopterin with haemoglobin levels. Significantly increased interferon-gamma and neopterin concentrations indicated persistent activation of cell-mediated immunity. Neopterin levels correlated significantly to interferon-gamma concentrations and inversely to haemoglobin levels. The data indicate an association between activated macrophages and the development of anaemia in patients with haematological neoplasias.     

Serum Neopterin and β2-Microglobulin Concentrations in Monoclonal Gammopathies

ABSTRACT Serum neopterin and β₂-microglobulin concentrations were investigated in 46 patients with multiple myeloma and in 28 patients with asymptomatic monoclonal gammopathy followed for long periods (median 9.6 years) and showing an absence of evolution. Seventy-two per cent of the patients with multiple myeloma showed β₂-microglobulin concentrations higher than 3 mg/1 with a mean of 6.84 mg/1, whereas all the patients with asymptomatic monoclonal gammopathies had concentrations lower than 3 mg/1 with a mean of 1.64 mg/1. Concerning serum neopterin concentrations, 91% of the patients with multiple myeloma had values with in pathological limits (>8 nmol/1) with a mean of 34 nmol/1, whereas all but one of the patients with asymptomatic monoclonal gammopathy had normal values with a mean of 5.19 nmol/1. The differences thus observed in these two groups of patients are highly significant (p<0.001). Serum neopterin concentration, unrelated to renal insufficiency, seems to be useful in the differentiation of malignant or benign asymptomatic monoclonal gammopathies.     

Plasma soluble interleukin-2-receptor in depression: relationships to plasma neopterin and serum IL-2 concentrations and HPA-axis activity

The present study examined the plasma concentration of the soluble interleukin-2-receptor (sIL-2R) in depressed subjects in relation to hypothalamic pituitary adrenal (HPA) axis function and plasma neopterin and serum IL-2 concentrations. Plasma sIL-2R concentration was significantly higher in depressed patients (n = 47) than in controls (n = 19). There were no significant correlations between plasma sIL-2R and severity of illness. In the depressed subjects, there was a highly significant relationship between plasma sIL-2R and neopterin concentrations. Depressed patients with pathologically increased plasma neopterin levels had significantly higher plasma sIL-2R values than those with normal serum neopterin. There were no significant relationships between plasma sIL-2R and indices of HPA-axis function in depression. There was no significant effect of dexamethasone administration on sIL-2R levels. Significantly more depressed subjects had measurable serum IL-2 levels than normal controls. Our data support the notion that a moderate activation of cell-mediated immunity may play a role in the pathophysiology of depression.     

腹部手术后细胞因子及其它介质的变化

目的：探讨腹部手术后细胞因子及其它介质的变化与意义。方法：动态观察2l例腹部外科患者术后外周血白细胞介素-6(IL-6)、新喋呤、降钙素基因相关肽((CGRP)、P物质(SP)、内毒素、一氧化氮(NO)、一氧化氮合酶(NOS)、脂质过氧化物(LPO)、总抗氧化能力(TAO)等变化。结果：术后当日、第3dIL-6，术后当日内毒素和第3、7d新喋呤均高于正常入。IL-6、内毒素术后当日明显高于其它时间点；新喋呤在术后较术前有所增高，癌症较之非癌症患者术后第3d新喋呤增高(P=0．057)，第7d显著增高。术后第7dSP明显低于正常组，且术后低干术前，第7d尤低；术后第3、7d CGRP明显高于正常组，且术后高于术前，第7d尤高，第14d高于其它时间点。NO于术后l周内明显降低，术后当日尤低，2周时接近正常组；NOS的变化趋势同NO；术后IPO及TAO进行性降低并低于术前，但LPO仍高于正常组。结论：中等以上腹部手术引起外周血IL-6、新喋呤和内毒素水平升高；其中恶性肿瘤患者术后新喋呤升高更明显。术后SP降低可能影响肠功能；CGRP升高便于组织存活。NO降低可能与组织低灌注有关。术后脂质过氧化作用减弱，总抗氧化能力亦降低。     

Association between biosynthesis of nitric oxide and changes in immunological and vascular parameters in patients treated with interleukin-2

Abstract Hypotension is a dose-limiting side effect of interleukin-2 (IL-2) therapy. This may be due to increased biosynthesis of the potent vasodilator nitric oxide (NO) induced by cytokines such as tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), which are known to be generated during IL-2 therapy. We describe the relationship between NO biosynthesis and changes in immunological and vascular parameters during IL-2 therapy in 13 patients with metastatic cancer. Plasma concentrations of neopterin and nitrite plus nitrate (NO_x) were higher in cancer patients prior to treatment compared with normal subjects (neopterin; 10·8±1·4 vs. 2·0±0·4 ng ml^-1, P<0·001: NO_x; 45±6 vs. 28±2 μM, P<0·005). Pretreatment TNF-α and IFN-γ plasma concentrations were not significantly different in cancer patients from those in controls. During infusion of IL-2 (18 times 10⁶ international units m^-2 per day for 5 days) these parameters increased, reaching maximal concentrations at day 3 for IFN-γ and day 5 for TNF-α, neopterin and NO_x. The maximal induced NO_x correlated with maximal TNF-α (r = 0·60, P<0·04), IFN-γ (r = 0·63, P<0·02) and neopterin (r = 0·66, P<0·01). As plasma NO_x concentrations increased, systolic blood pressure fell, reaching a minimum at day 3 despite a continued rise in NO_x concentrations. These changes were accompanied by a continuous increase in pulse rate throughout the infusion period. These findings indicate that induction of NO biosynthesis contributes to hypotension induced during IL-2 therapy. Inhibitors of NO synthase may be useful in limiting toxicity, thus allowing administration of higher and possibly more efficacious doses of this cytokine in the treatment of cancer.     

Modulation of lymphocyte and monocyte activity after intravenous immunoglobulin administration in vivo

In 12 patients with primary hypogammaglobulinaemia we investigated the in vivo effect of one bolus injection (400 mg/kg) of intravenous immunoglobulin (IVIG) on lymphocyte subsets and monocytes in peripheral blood, on plasma levels of soluble factors reflecting monocyte and lymphocyte activity and on lymphocyte proliferation and generation of reactive oxygen species (ROS) from monocytes analysed in vitro. Several immunological changes were induced by IVIG infusion. First, there was a significant decrease in CD4⁺/CD8⁺ lymphocyte ratio in peripheral blood, reflecting a significant increase in circulating numbers of CD8⁺ lymphocytes. Second, although there was no significant change in plasma levels of soluble CD8 antigen, there was a significant decrease in soluble CD8 antigen/CD8⁺ lymphocyte ratio, suggesting a down-regulation of CD8⁺ lymphocyte activity. Third, there was a significant increase in plasma levels of neopterin, suggesting in vivo activation of monocytes/macrophages. Fourth, the was a down-modulation of mitogen-stimulated lymphocyte proliferation in vitro, and this down-regulation was significantly correlated with the increase in plasma neopterin levels. Finally, there was a significant decrease in zymosan-stimulated, but not in phorbol myristate acetate-stimulated, ROS generation from monocytes as evaluated by nitroblue tetrazolium reduction. The ability of IVIG administration in vivo to down-modulate lymphocyte proliferation and ROS generation from monocytes in patients with persistent immune activation may be relevant for the clinical effects of IVIG in a variety of immune-mediated disorders.     

寻常型银屑病血清新喋呤水平的测定

用酶联免疫分析法测定３０例寻常型银屑病患者的血清新喋呤水平。结果表明，患者组的血清新喋呤水平显著高于对照组（Ｐ＜０．００１），进行期显著高于静止期（Ｐ＜０．００１），治疗前显著高于治疗后（Ｐ＜０．００１），且新喋呤水平随病情活动而变化，与皮损严重程度呈显著正相关关系（ｒ＝０．７９５６，Ｐ＜０．００１）。提示银屑病的发病与细胞免疫的激活有关，新喋呤水平测定可作为监测该病活动和治疗效果的指标。     

Serum neopterin levels in women with preeclampsia: a systematic review

ABSTRACT

Objective: Neopterin is a pteridine that is produced following activation of human macrophages upon stimulation with the cytokine interferon-gamma. Several studies suggest its association with preeclampsia and the purpose of the present study is to evaluate this assumption. Methods: We searched the Medline (1992–2018), Scopus (1993–2018) and Google Scholar (1993–2018) databases. All articles that evaluated serum neopterin levels in patients with preeclampsia were held eligible for inclusion, regardless of the trimester of pregnancy in which the measurement was performed. Case reports, animal studies and previous reviews were excluded. Results: A total of 10 studies were finally included in the present review, with a total number of 3,529 pregnant women. Among them 446 were diagnosed with preeclampsia. The majority of included studies reported that serum neopterin was significantly higher in patients with preeclampsia, compared to normotensive pregnant women (p < .05). One study reported that serum levels seem to correlate with the severity of the disease; as patients with HELLP had significantly higher values of neopterin compared to patients with mild and severe preeclampsia. None of the included studies proposed a cut-off value that would help assess the predictive accuracy of this protein for the detection of preeclampsia. Conclusion: Although current data seem to be promising, neopterin remains far from being used in current clinical practice as a biomarker that would help predict and follow-up patients that develop preeclampsia. Future studies are needed, to determine the optimal timing for its measurement and to propose potential cut-off values that would help in this direction.     

联合检测血清脂蛋白相关磷脂酶-A2(LP-PLA2)及新蝶呤(NPT)在急性冠脉综合征患者血清中的表达及意义

目的:通过研究急性冠脉综合征患者血清脂蛋白相关磷脂酶-A2 (LP-PLA2)及新蝶呤(NPT)的表达及其含量的变化规律,以期探讨两者联合检测在急性冠脉综合征中的临床诊断价值.方法:用酶联免疫法检测46例急性冠脉综合征(ACS)患者血清中LP-PLA2及NPT水平,其中:非ST段抬高的心肌梗死组(NSTEMI)8例,S...     

儿童乙型病毒性肝炎病毒携带者血清新蝶呤水平分析

目的研究儿童乙型病毒性肝炎病毒(HBV)携带者血清新蝶呤水平变化及其与HBV复制的关系。方法采用酶联免疫吸附试验(ELISA)法和实时荧光定量PCR法分别检测150例儿童HBV携带者和60名健康儿童的血清新蝶呤水平、HBV DNA载量。结果慢性HBV携带者血清新蝶呤水平明显高于非活动性HBsAg携带者和健康儿童,差异有统计学意义(均P0.05);非活动性HBsAg携带者和健康儿童的血清新蝶呤水平差异无统计学意义(P0.05);血清新蝶呤水平与HBV DNA载量在统计学上无显著相关性(r=0.131,P0.05)。结论在儿童HBV携带者中,慢性HBV携带者比非活动性HBsAg携带者体内更容易引起细胞免疫激活,慢性HBV携带者在随访监测中更应被关注,其血清新蝶呤水平升高能提示病毒复制,但不反映病毒复制活跃程度。