Dynamics of lymphocyte subsets in children living in an area polluted by polychlorinated biphenyls.

Immune system development, particularly in the pre-natal and early post-natal periods, has far-reaching health consequences during childhood, as well as throughout life. Exposure to poly-chlorinated biphenyls (PCBs) during pre-natal and early life has been previously associated with changes in the incidence of infectious and allergic diseases in children, and humoral immunity alterations. Lymphocyte immunophenotyping is an important tool in the diagnosis of immunologic and hematologic disorders. This study used a lysed whole blood method for analysis of lymphocyte sub-populations in samples from children born and living in two districts: a highly-contaminated area (Michalovce) and one (Svidnik/Stropkov) with ≈ 2-fold lower environmental PCB levels. The percentages of B-lymphocytes (CD19(+)), activated HLADR(+)CD19(+) cells, and CD8(+) T-lymphocytes significantly increased at 6- and 16-months-of-age in both selected regions as compared to in cord blood values (p < 0.001). Levels of CD3(+) cells increased significantly (from 61 to 65%) in samples from Michalovce (p < 0.01). Levels of CD4(+) T-lymphocytes declined 10% among 16-month-olds in both regions (Michalovce at p < 0.001 and Svidnik/Stropkov at p < 0.01). Natural killer (NK) cell levels decreased 50% in Michalovce 6- and 16-month-old children and 42% among 6-month-olds in Svidnik/Stropkov (p < 0.001). Compared with the less-contaminated region, Michalovce samples showed significantly higher expression of CD3(+) T-lymphocytes, B-lymphocytes, and activated B-lymphocytes, whereas NK cells were less expressed. Even after adjustment for selected covariates, e.g., maternal cigarette smoking, age, parity, ethnicity, birth weight, and gender of infant, the levels of CD19(+), HLADR(+)CD19(+), and CD3(-)CD(16 + 56)(+) cells were seen to remain significantly different between the districts. These results showed that early-life environmental PCB exposure was associated with fluctuations in major lymphocyte subsets in children, suggesting that there is a post-natal immune system response to PCB exposures.

The relationship between cell surface markers, cytokines, ageing, and cigarette smoking.

The purpose of this study was to investigate the modulation of selected cell surface markers and proinflammatory cytokines production in relation to ageing, and cigarette smoking. The analysis of cell surface receptors was performed by the flow cytometry and cytokines levels were evaluated by the sandwich enzyme immunoassays. We found a decreased expression of CD69, CD28, CD11b, CD95 markers in old population compared to young people (p<0.05; p<0.001). The memory CD45RO lymphocytes were markedly expanded in older population in comparison to young donors (12.93+/-5.92 %, p<0.001) and the selectin CD62L was significantly increased on granulocytes in aged people (p<0.05). Our findings demonstrated an augmented level of CD3 and CD28 on lymphocytes in smokers (p<0.05; p<0.005). The significant depression of CD16+56 molecule was recorded in smokers (10.86+/-0.80%) when compared to non-smokers (14.44+/-0.46; p<0.05). Our results showed a significantly diminished levels of interleukin (IL)-1beta (1.93+/-0.48 pg/ml), and increased levels of IL-6 and tumor necrosis factor (TNF)-alpha in elderly population compared to young people (p<0.05; p<0.001). The present data support previous suggestions that senescence and cigarette smoking may contribute to changes in the immune system activity, resulting in altered cell surface marker expression and cytokine levels (Tab. 1, Fig. 3, Ref. 81). Full Text (Free, PDF) www.bmj.sk.

DNA repair and cyclin D1 polymorphisms and styrene-induced genotoxicity and immunotoxicity.

1-SO-adenine DNA adducts, DNA single-strand breaks (SBs), chromosomal aberrations (CAs), mutant frequency (MF) at the HPRT gene, and immune parameters (hematological and of humoral immunity) were studied in styrene-exposed human subjects and controls. Results were correlated with genetic polymorphisms in DNA repair genes (XPD, exon 23, XPG, exon 15, XPC, exon 15, XRCC1, exon 10, XRCC3, exon 7) and cell cycle gene cyclin D1. Results for biomarkers of genotoxicity after stratification for the different DNA repair genetic polymorphisms showed that the polymorphism in exon 23 of the XPD gene modulates levels of chromosomal and DNA damage, HPRT MF, and moderately affects DNA adduct levels. The highest levels of biomarkers were associated with the wild-type homozygous AA genotype. The exposed individuals with the wild-type GG genotype for XRCC1 gene exhibited the lowest CA frequencies, compared to those with an A allele (P < 0.05). Cyclin D1 polymorphism seems to modulate the number of leukocytes and lymphocytes in the analyzed subjects. The number of eosinophiles was positively associated with XPD variant C allele and negatively with XRCC1 variant A allele (P < 0.05) and XPC variant C allele (P < 0.05). Immunoglobulin IgA was positively associated with an XRCC3 variant T allele (P < 0.01) and negatively with XPC variant C allele (P < 0.05). Both C3- and C4-complement components were lower in individuals with XRCC3 CT (P < 0.05) and TT genotypes (P < 0.01). Adhesion molecules sL-selectin and sICAM-1 were associated with XPC genotype (P < 0.05). Individual susceptibility may be reflected in genotoxic and immunotoxic responses to environmental and occupational exposures to xenobiotics.

Different patterns of serum interleukin 10 response to treatment with anti-tumor necrosis factor alpha antibody (infliximab) in Crohn's disease.

Administration of anti-tumor necrosis factor antibody (anti-TNF, infliximab) down-regulates T helper 1 (Th 1) cytokines production in intestinal mucosa of patients with Crohn's disease (CD). Interleukin 10 (IL-10) is thought to be involved in CD pathogenesis through regulation of the Th 1 response. The aim of this study was to determine the IL-10 response in CD patients treated with anti-TNF. Fourteen patients with active CD received 5 mg/kg of infliximab; clinical activity assessed by Crohn's Disease Activity Index (CDAI), alpha1-acid glycoprotein and serum IL-10 were determined before and after treatment, in month 0, 1 and 5. In the group with a good clinical response, IL-10 levels diminished significantly in month 1 (p<0.05) and remained decreased in month 5. The group with a lower response showed a significant increase in IL-10 levels in month 1 (p<0.05). alpha1-acid glycoprotein levels obtained before treatment were significantly elevated in the group with a good clinical response (p<0.05) and a significant decrease in month 1 was observed in this group (p<0.05). These observations suggest that a pattern of IL-10 response might be related to the clinical response to anti-TNF treatment in CD.

Effects of occupational exposure to styrene on expression of adhesion molecule on leukocytes.

Styrene is an indispensable chemical extensively used in plastic and synthetic rubber industries. Styrene is known to produce various types of hepatotoxic, neurotoxic, and genotoxic effects. Styrene may be immunotoxic by both direct and indirect mechanisms. Measurement of adhesion molecules is a new tool for the investigation of immune system modulation. The aim of this study was to evaluate the association of the expression of the adhesion molecules CD11a, CD11b, CD18, CD54, CD49d, and CD62-L in white blood cells and levels of soluble adhesion molecules ICAM-1 and L-selectin in serum with occupational exposure to styrene. Analyses by flow cytometry revealed elevated levels of most of the assessed adhesion molecules on surfaces of lymphocytes, monocytes, and granulocytes. Expression of the adhesion receptor antigens CD11a on lymphocytes, CD11b on monocytes, and CD18 on granulocytes were unaffected. Workers exposed to styrene had decreased concentrations of sICAM-1 and no changes in concentrations of sL-selectin. Styrene exposure appears to increase activation of the immune system and alter leukocyte adherence. This interaction is a critical first step in immune stimulation and leukocyte-endothelial interaction.

Biomonitoring of occupational exposure to styrene in a plastics lamination plant.

A comprehensive approach to biological monitoring of 44 workers occupationally exposed to styrene in a hand lamination plant was performed by using several end-points: styrene in workplace air, styrene in exhaled air, styrene in blood, DNA strand breaks (SBs) and oxidised bases in mononuclear leukocytes, chromosomal aberrations in lymphocytes, immune parameters and genotyping of polymorphic genes of some xenobiotic-metabolizing enzymes (CYP 1A1, EPHX, GSTM1 and GSTP1). We found a significantly higher number of DNA SBs, measured by a modified comet assay, in mononuclear leukocytes of the styrene-exposed workers compared with results from 19 unexposed controls (P<0.001). A fairly strong correlation was observed between SBs and years of exposure (P<0.001, r=0.545). The styrene-exposed workers also showed a significantly increased frequency of chromosomal aberrations (P<0.0001 for highly exposed group, P<0.004 for medium-exposed group, and P=0.0001 for low-exposed group). The proliferative response of T-lymphocytes stimulated with concanavalin A was significantly suppressed in people exposed to styrene (P<0.05). We recorded a significant increase of the percentage of monocytes in differential white blood cell counts in the exposed group (P<0.05). Using flow cytometry, we found an increased expression of adhesion molecules CD62L, CD18, CD11a, CD11b, CD49d and CD54 in the exposed workers as compared with the control group (P<0.05).

[Successful modification of human intestinal microflora with oral administration of lactic acid bacteria]. / Prospesná modifikácia crevnej mikroflóry cloveka perorálne podávanými baktériami mliecneho kysnutia.

Lactic acid bacteria in food can transiently colonize the intestine and exert health beneficial (probiotic) effects. These include: 1. Lactose digestion, improvement of diarrheal disorders (including traveller's diarrhea), prophylaxis of intestinal and urogenital infections--as a result of formation or reconstruction of a balanced indigenous microflora. 2. Inhibition of the mutagenicity of the intestinal contents and reduction of the incidence of intestinal tumours. 3. Immunomodulatory effects resulting in the improved host resistance. 4. Depression of the serum cholesterol level. The most of these effects were observed in a group of adult subjects administered daily by a lyophilized Enterococcus faecium M-74 in the form of waffles (Dr. Ebi) during nine weeks of a double blind placebo controlled clinical trial. The bacterium temporarily colonized the host intestine and its secretion in stool persisted for six weeks after the last dose. The mean activities of beta-D-glucuronidase in stools of subjects given waffles containing enterococci were reduced comparing to stools of placebo subjects. After six weeks of daily eating the waffles with enterococci, an increased production of superoxide and other reactive oxygen intermediates by peripheral neutrophils was observed. The increase corresponded in time with an elevated formation of IgG by peripheral blood mononuclear cells after polyclonal activation with mitogenes. Higher activities of myeloperoxidase and elastase in peripheral neutrophils were also ascertained during eating of waffles containing of E. faecium M-74. Hence, intake of E. faecium M-74 in the form of waffles may have an significant immunostimulatory effect on both phagocytosis performed by neutrophils and antibody production. (Tab. 6, Ref. 29.)

[Vascular endothelium as a factor in information transfer between the cardiovascular and immune systems]. / Cievny endotel ako operátor prenosu informácií medzi kardiovaskulárnym a imunitným systémom.

In health, the vascular endothelium forms a multifunctional interface between the circulating blood and various tissues and organs of the body. It constitutes a selectively permeable barrier for macromolecules, as well as a nonthrombogenic and nonadhesive container that actively maintains the fluidity of blood. It is a metabolically active endocrine organ, serving as the source of multiple factors and mediators that are critical for normal homeostasis. These include vasodilators (nitric oxide, prostacyclin, endothelium-derived hyperpolarizing factor), vasoconstrictors (endothelin-1, thromboxane A2, prostaglandin H2 and components of the renin angiotensin system), various pro- and antithrombotic factors (e.g. tissue factor, platelet activating factor--PAF, von Willebrand factor), fibrinolytic activators and inhibitors (e.g. tissue plasminogen activator, plasminogen activator inhibitor-1), potent arachidonate metabolites (prostanoids), leukocyte adhesion molecules (e.g. E-selectin, P-selectin, intercellular adhesion molecule-1--ICAM-1, vascular cell adhesion molecule-1--VCAM-1), and multiple cytokines with activities of growth stimulators and inhibitors, transforming growth factors, proinflammatory and antiinflammatory mediators, tumour necrosis factors and chemotactic factors (chemokines). Besides these essential activities controlling the cardiovascular system, the endothelial cells represent an important part of the immune system as well. They have a pivotal role in the initiation and development of defensive and damaging inflammatory responses. Therefore endothelium can be considered as being the central equipment for the mutual exchange of life important information between the cardiovascular and immune systems. This in turn is leading to rapid advances in understanding the pathogenesis of some of the most serious and most common diseases, including inflammation, atherosclerosis and hypertension. (Tab. 7, Ref. 89.)

Links between prolonged exposure to xenobiotics, increased incidence of hepatopathies, immunological disturbances and exacerbation of latent Epstein-Barr virus infections.

Disturbances of several humoral and cellular immune parameters are significantly increased in individuals exposed to chemical pollutants. Moreover, exacerbations of the latent Epstein-Barr virus (EBV) infection were more frequently observed in the chemically exposed group than in the control groups. A significant correlation was seen between EBV exacerbations and the increased number of eosinophils, T-lymphocyte rosette formation and the respiratory burst of polymorphonuclear blood cells. Possible links between hepatopathy due to xenobiotics exposition, immunological disturbances and EBV exacerbation are discussed, including a putative role of EBV-induced (autocrine) cytokines.

[Selected immunologic indicators in malignant bone tumors]. / Vybrané imunologické ukazatele pri kostních maligných nádoroch.

In patients with the malignant tumor of bone (17 osteosarcomas, 8 Ewing tumors) longterm observations were made, and namely at the beginning of the disease, after the surgical removal of the tumor, during chemotherapy and in the terminal phase of the disease. The observations concentrated on the following selected immunology parameters: active lymphocytes T, lymphocytes T, lymphocytes B, large granular lymphocytes, IgG, IgA, IgM and circulating immune complexes. In non-treated patients prior to diagnosing the disease, reduction of active lymphocytes T was found out while the total lymphocytes T remained unchanged. However, no significant differences were found out between benign and malignant tumors. The surgical removal of the tumor results in the change in imunologic indicators, the increase of active lyphocytes T, lymphocytes T and the decrease in the circulating immune complexes. The change is of temporary nature, the subsequent deterioration is caused by both the progression of the disease and chemotherapy. The values of immunoglobulins and lymphocytes B fluctuated during the whole course of the disease in physiological levels. The observation of active lymphocytes T and lymphocytes T can be used for monitoring of the immunosuppression in cytostatic treatment. The levl of IgG is differentially diagnostically used to distinguish between the tumor and inflammatory processes.