Effects of environmental lead exposure on T-helper cell-specific cytokines in children

Lead (Pb) may alter T-lymphocyte reactivity in situ by preferentially enhancing the development of T-helper 2 (T(H)2)- and inhibiting T(H)1-lymphocyte development. These effects could result in dysregulation of the presence/availability of T(H)1- and T(H)2-associated cytokines. The aim of this study was two-fold, that is, to assess whole blood Pb levels in schoolchildren from Taiwanese communities that varied in degree of potential for Pb exposure and then ascertain if there were relationships between Pb exposure and changes in levels of key T(H)1 and T(H)2 cytokines. Grades 5 and 6 students were selected from four different community schools, i.e., one from: urban area with new homes; urban area with old homes; rural site with old homes; and area located near an oil refinery. Students at each site were further divided into healthy and respiratory allergy subgroups. Blood was collected and whole blood Pb levels and serum interferon (IFN)-γ, interleukin (IL)-12, -4, and -5 levels were determined. The results indicate no differences in whole blood Pb levels (<4 μg/dl) among students from urban and rural sites; these values were similar in the healthy and allergic subjects. Serum T(H)1 and T(H)2 cytokine levels also did not differ among/within the groups. In contrast, refinery children had significantly increased Pb levels (5.2-8.8 μg/dl) relative to any of the other sets' levels. Of these, children with allergies had serum T(H)2 cytokine levels significantly higher and T(H)1 cytokine levels significantly lower than their healthy counterparts. Oddly, though having elevated Pb levels, healthy refinery students did not display altered T(H)1 or T(H)2 cytokine levels relative to control student values. From this, we conclude that substantively increased whole blood Pb levels may promote T(H) cell dysregulation and alter the availability of key T(H)1 and T(H)2 cytokines, effects that could ultimately contribute to development of pulmonary allergic diseases.     

Effects of environmental lead exposure on T-helper cell-specific cytokines in children

Lead (Pb) may alter T-lymphocyte reactivity in situ by preferentially enhancing the development of T-helper 2 (T_H2)- and inhibiting T_H1-lymphocyte development. These effects could result in dysregulation of the presence/availability of T_H1- and T_H2-associated cytokines. The aim of this study was two-fold, that is, to assess whole blood Pb levels in schoolchildren from Taiwanese communities that varied in degree of potential for Pb exposure and then ascertain if there were relationships between Pb exposure and changes in levels of key T_H1 and T_H2 cytokines. Grades 5 and 6 students were selected from four different community schools, i.e., one from: urban area with new homes; urban area with old homes; rural site with old homes; and area located near an oil refinery. Students at each site were further divided into healthy and respiratory allergy subgroups. Blood was collected and whole blood Pb levels and serum interferon (IFN)-γ, interleukin (IL)-12, -4, and -5 levels were determined. The results indicate no differences in whole blood Pb levels (<4 µg/dl) among students from urban and rural sites; these values were similar in the healthy and allergic subjects. Serum T_H1 and T_H2 cytokine levels also did not differ among/within the groups. In contrast, refinery children had significantly increased Pb levels (5.2–8.8 µg/dl) relative to any of the other sets’ levels. Of these, children with allergies had serum T_H2 cytokine levels significantly higher and T_H1 cytokine levels significantly lower than their healthy counterparts. Oddly, though having elevated Pb levels, healthy refinery students did not display altered T_H1 or T_H2 cytokine levels relative to control student values. From this, we conclude that substantively increased whole blood Pb levels may promote T_H cell dysregulation and alter the availability of key T_H1 and T_H2 cytokines, effects that could ultimately contribute to development of pulmonary allergic diseases.     

Serum cytokines and increased total serum IgE in alcoholics.

BACKGROUND: It has been reported that total serum IgE is increased in alcohol abusers, but the mechanisms responsible are not known. Production of IgE depends on B-cell stimulation by both antigens and some cytokines, particularly IL-4 and IL-13. Chronic alcoholism and alcoholic liver disease are accompanied by changes in cytokine production. AIM OF THE STUDY: To evaluate if IgE increase in alcoholics could be associated to a ethanol-induced imbalance of the cytokine profile. PATIENTS AND METHODS: A total of 65 patients (53 males and 12 females, aged 47 +/- 12 years), admitted to the hospital because of ethanol abstinence symptoms entered the study. On admission, total serum IgE was measured by chemiluminescent EIA and serum IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, and interferon-gamma were measured by ELISA. Data were compared with those of 40 healthy control subjects. RESULTS: Serum IgE, IL-6, IL-8, IL-10, IL-12, and IL-13 were found to be high in alcoholic patients compared with healthy volunteers. Some parallelism was observed between serum IgE and both serum IL-10 and IL-13 were increased in alcoholics. CONCLUSIONS: Total serum IgE elevation in alcoholics with abstinence syndrome is accompanied by an increase of some type 2 cytokines. Ethanol-induced alterations in the cytokine profile may contribute to increased IgE levels in alcoholics.     

癫癎患者血清细胞因子水平的研究

目的：探讨细胞因子与癫癎发病的关系。方法：采用酶联免疫吸附法（ＥＬＩＳＡ） 对５８ 例癫癎患者及４２ 例正常对照血清可溶性白细胞介素２ 受体（ｓＩＬ２Ｒ） 及肿瘤坏死因子（ＴＮＦ） 水平进行了检测。结果：癫癎组血清ｓＩＬ２Ｒ 及ＴＮＦ 水平显著高于正常对照组,血清ｓＩＬ２Ｒ 及ＴＮＦ 水平变化与癫癎类型无关,抗癫癎药物对血清ｓＩＬ２Ｒ 及ＴＮＦ 水平无明显影响。结论：癫癎患者存在内在的细胞免疫功能紊乱,其单核—巨噬细胞及Ｔ淋巴细胞处于激活状态。     

Characterization of serum and liver lipids of gallstone-forming humans.

Liver biopsy and serum specimens obtained from patients with cholesterol gallstones and from a control group were analysed for their different lipids and lipoprotein fractions. The ratio of free cholesterol to esterified cholesterol (CF/CE) was significantly (P less than 0.001) higher in the livers of gallstone-forming patients. There was no significant difference in the levels of total lipids, total cholesterol, phospholipids and glycerides. Beta-lipoprotein fraction (LDL) was higher in gallstone-forming patients. It is concluded that the decrease in esterified cholesterol of gallstone-formers may provide an important clue to an understanding of the physiology and chemistry of stone-formation in humans.     

Distinct serum cytokines in AIDS-related skin diseases

To determine whether common skin diseases associated with human immunodeficiency virus (HIV) were distinguishable based on the pattern of serum cytokine expression, we studied patients with psoriasis, pruritus, and Kaposi's sarcoma (KS) for levels of tumor necrosis factor (TNF)-alpha, interferon-gamma (IFN-y), interleukin (IL)-10, and IL-4. Thirty-two HIV-positive (HIV+) patients including 8 with KS, 11 with psoriasis, and 13 with pruritus along with 16 HIV-negative subjects with psoriasis were studied. IFN-gamma levels were highest in sera of HIV+ patients with psoriasis (p = 0.040). By contrast, TNF-alpha and IL-10 levels were highest in sera of HIV+ patients with pruritus (p = 0.012). Detectable levels of all cytokines in these patients were remarkably higher than for healthy adults. These results suggest that common skin diseases associated with HIV infection and AIDS can be distinguished by the production of unique cytokines.     

Impaired production of proinflammatory cytokines in response to lipopolysaccharide (LPS) stimulation in elderly humans.

Ageing is associated with decreased resistance to bacterial infections and concomitant increased circulating levels of inflammatory cytokines. The purpose of the present study was to research age-related changes in levels of early mediators of the acute-phase response in whole blood supernatants following LPS stimulation, representing an ex vivo model of sepsis. Levels of tumour necrosis factor-alpha (TNF-alpha), IL-1beta and IL-6 in whole blood supernatants were measured after in vitro LPS stimulation for 24 h in 168 elderly humans aged 81 years from the 1914 cohort in Glostrup, Denmark and in 91 young controls aged 19-31 years. Levels of TNF-alpha and IL-1beta were significantly lower in elderly humans compared with young controls, whereas no difference was detected with regard to IL-6. Elderly humans with low body mass index had the lowest levels of IL-1beta. Young women had lower levels of proinflammatory cytokines compared with young men, but this difference was blurred by ageing. No relation was found between circulating plasma levels of TNF-alpha and levels after in vitro LPS stimulation. In conclusion, decreased production of TNF-alpha and IL-1beta after exposure to LPS may reflect impaired host defence against infections in the elderly and be of importance in elderly humans with underlying health disorders. However, the clinical relevance is questionable in healthy elderly people because decreased levels were found compared with young men but not compared with young women.     

丙型肝炎病毒感染者血清细胞因子的检测

目的 探讨丙型肝炎病毒（ＨＣＶ）感染慢性化的宿主免疫机制。方法 用酶联免疫吸附实验测定了１８例慢性ＨＣＶ感染者、１１例正常对照和１０例慢性ＨＢＶ感染者的Ｔ辅助淋巴细胞（Ｔｈ０细胞因子ＩＦＮ－γ,ＩＬ－２,ＩＬ－４和ＩＬ－１０的血清浓度。结果 ＨＣＶ感染者的ＩＬ－２（Ｔｈ１细胞因子）、ＩＬ－４的ＩＬ－１０（Ｔｈ２细胞因子）较正常对照均明显增高（Ｐ〈０．０５,Ｐ〈０．０２５,Ｐ〈０．００１）,但以Ｔｈ     

Hypoxemia increases serum interleukin-6 in humans

 Serum concentrations of interleukin (IL) 1 beta, IL-1 receptor antagonist (IL-1ra), IL-6, tumor necrosis factor (TNF) alpha, and C-reactive protein (CRP) were determined in ten healthy men at sea level and during four days of altitude hypoxia (4350m above sea level). The mean (SD) arterial blood oxygen saturations were 78.6 (7.3)%, 82.4 (4.9)%, and 83.4 (5.3)% in the first, second, and third days at altitude, respectively. A symptom score of acute mountain sickness (AMS) revealed that the subjects had mostly light symptoms of AMS. Mean serum IL-6 increased from 1.36 (1.04) pg × ml^–1 at sea level to 3.10 (1.65), 4.71 (2.81), and 3,54 (2.17) pg × ml^–1 during the first three days at altitude, and to 9.96 (8.90) pg × ml^–1 on the fourth day at altitude (ANOVA p =0.002). No changes occurred in serum concentrations of IL-1 beta, IL-1ra, TNF alpha, or CRP. The serum IL-6 were related to SaO₂, ( r =–0.45, p =0.003), but not to heart rates or AMS scores. In conclusion, human serum concentrations of IL-6 increased during altitude hypoxia whereas the other proinflammatory cytokines remained unchanged. The major role of IL-6 during altitude hypoxia seem not to be mediation of inflammation, instead, the role of IL-6 could be to stimulate the erythropoiesis at altitude. Accepted: 30 May 1997     

Maternal serum levels of pro-inflammatory cytokines in missed and threatened abortion

PROBLEM: A study of association between pro-inflammatory cytokines, and missed and threatened abortions with good outcome has been performed. METHOD OF STUDY: The presence of pro-inflammatory cytokines, namely interleukin (IL)-8 and IL-12 and the soluble interleukin-2 receptor (SIL-2R) was investigated in maternal serum of 12 patients with threatened abortion twice (at admission and discharge), 14 patients with missed abortion, 14 women with healthy first-trimester pregnancy, and 14 normal non-pregnant women, using specific enzyme-linked immunosorbent assays. RESULTS: SIL-2R and, in particular, IL-12 was detected with significantly higher levels in missed abortion group compared with all other groups. IL-8 was detected with no significant difference among all the groups studied. CONCLUSIONS: In spite of caution due to the small sizes of the subject samples, these results support a role of the immune system in the first trimester pregnancy and hypothesize that missed abortion may be associated with an enhanced Th1 reactivity, whereas threatened abortion with good outcome resembles the normal pregnancy with a non-enhanced Th1 reactivity.     

Comparison of human fecal and serum parvo-like viruses.

Parvovirus-like particles found in the sera of two blood donors had the size and appearance on electron microscopy of a virus (B19) found in the serum of a blood donor by Cossart et al. (1975), and those of a virus found in the feces of a normal subject. Antibody to these viruses was detected by immune electron microscopy and immunoelectro-osmophoresis in the sera of 50 children aged 10 to 15 years. Of these, 36% had antibody to the fecal virus, 36% had antibody to B19, and 54% had antibody to the two other serum viruses. The results of these tests suggest that serologically the three serum viruses were similar to one another, but that the fecal virus was distinct. The two blood donors had nonspecific symptoms at the time of viremia. Both donors had developed immunoglobulin M antibody to the virus when tested 3.5 and 4.5 weeks later, but no viruses were detected in the feces or urine.     

Demonstration of serum antibodies to Cryptosporidium sp. in normal and immunodeficient humans with confirmed infections.

Antibodies to Cryptosporidium sp. were detected in sera from 12 immunocompetent individuals recovered from cryptosporidiosis and from 5 subjects with an acquired immunodeficiency syndrome and persistent cryptosporidiosis by an indirect immunofluorescent (IIF) test. Marked seroconversion accompanied recovery from infection in immunocompetent individuals, and their IIF titers remained high (1:40 to 1:640) for at least 1 year. No antibodies to Cryptosporidium sp. were detected in sera from two subjects with hypogammaglobulinemia, normal T-cell function, and persistent cryptosporidiosis or in sera from individuals not previously exposed to Cryptosporidium sp. Very little or no cross-reactivity with the other coccidia--Toxoplasma, Sarcocystis, and Isospora spp.--occurred in the IIF test procedure. The application of this IIF procedure, along with recently developed techniques to detect oocysts in the feces, should provide the basis for a more accurate assessment of the number of individuals within any subject group with previous and active Cryptosporidium infections.     

Protective properties and haemagglutinins in serum from humans and in serum from mice injected with a new polyvalent Pseudomonas vaccine.

Mice given single injections of a polyvalent pseudomonas vaccine produced anti-pseudomonas haemagglutinins against the 16 component immunogens of the multivalent vaccine. Mice passively immunized with sera from vaccinated mice were protected against lethal challenge by 8/10 strains of Ps. aeruginosa of homologous serotype. Protection by the serum was inversely proportional to the virulence of the challenge strains. Anti-pseudomonas haemagglutinins were always present in sera which passively protected mice against pseudomonas infection. Low levels of anti-pseudomonas haemagglutinins were present in some sera which failed to passively immunize mice against pseudomonas infection. Anti-pseudomonas haemagglutinins and antibodies involved in passive protection were mainly in the IgM fractions of mouse serum. Control human sera contained anti-pseudomonas haemagglutinins against most serotypes of Ps. aeruginosa. Sera from patients with burns contained high levels of anti-pseudomonas haemagglutinins against some but not all serotypes of Ps. aeruginosa. Sera from both controls and patients with burns passively protected mice against pseudomonas infection.     

Establishment of T cell-specific and natural killer cell-specific unigene sets: towards high-throughput genomics of leukaemia.

We report the establishment of highly non-redundant unigene sets consisting of cDNA clones derived from T lymphocytes and natural killer cells. Each set consists of 10 506 and 13 409 clones, respectively, arrayed on nylon membranes in duplicate. The sets provide an excellent tool for genome-wide gene expression analysis studies in immunology research.     

MKR转基因糖尿病小鼠血糖血脂与血清炎症因子CRP、IL-6、TNF-α的相关性分析

2型糖尿病发病机制较为复杂,至今尚未完全阐明,炎症反应发病学说备受关注,这种炎症反应被认为是一种亚临床炎症,是导致胰岛素抵抗、胰岛β细胞损伤和血管内皮细胞功能紊乱,从而对糖尿病及其慢性血管并发症的发生发展起着重要作用[1].     

Basal cell-specific and hyperproliferation-related keratins in human breast cancer.

In normal breast tissue and in noninvasive breast carcinomas, various keratin-14 antibodies were reactive predominantly with the basal/myoepithelial cell layer, although mainly in terminal and larger ducts luminal cells sometimes also were stained. A similar reaction pattern was found with an antibody directed against keratin 17, although this antibody was more often found negative than keratin 14 in the pre-existing myoepithelial cells in intraductal carcinomas. Furthermore antibodies reactive with hyperproliferation-related keratins 6 and 16 were used. One of these (LL025) was completely negative in normal breast tissue and noninvasive breast carcinomas. However 10% of the invasive carcinomas were diffusely or focally positive with this latter antibody, while in 18 of 115 cases of invasive breast carcinomas studied, a basal cell phenotype was detected. A relatively high concordance was found between the carcinomas immunostaining with the basal cell and the hyperproliferation-related keratins, but not between these markers and the proliferation marker Ki-67. This supports the conclusion that basal cells in breast cancer may show extensive proliferation, and that absence of Ki-67 staining does not mean that (tumor) cells are not proliferating.     

Negative emotions and cytokines in maternal and cord serum at preterm birth

Problem This study investigates whether affectivity differs between mothers delivering preterm and term and whether maternal and umbilical cord serum cytokines differ between these groups. Further, whether there are associations between mothers’ emotions and maternal and cord cytokines at preterm and term birth. Method of study Twenty‐seven mothers delivering preterm and 37 mothers delivering at term reported positive/negative affect and previous depressive symptoms during pregnancy. Blood samples from mothers in labor and cord samples (23 preterm and 33 term) were analyzed for cytokines. Results Maternal IL‐8 was lower at preterm delivery compared with term. In the preterm group only, associations were found between negative emotions and maternal IL‐6, IL‐8 and cord IL‐6, IL‐8, IL‐10, IL‐13, and IL‐18. Conclusion The findings indicate associations in preterm delivery between negative emotions and both maternal and neonate immune activity. Future studies should investigate whether such associations are part of the etiology of preterm delivery.