Prolonged reduction of salivary immunoglobulin A (sIgA) after a major academic exam.

OBJECTIVE: In a previous study we observed a continuous reduction of salivary IgA concentration ([sIgA]) during a period of academic stress. This reduction of sIgA concentration exceeded the stress period by at least 1 week. The present study aimed to replicate and extend our previous finding. In particular, we wanted to examine the time of recovery of [sIgA] alterations associated with academic stress. METHOD: Twenty-seven participants in a major medical exam and 27 controls not participating in any exam during the study provided daily saliva samples (immediately after awakening), from the 6th day prior to their last exam until the 14th day afterwards, for analysis of salivary IgA. Data were averaged for the last weeks of exams and the first and second week after exams, respectively. RESULTS: A prolonged reduction of sIgA in exam students as compared to controls was observed. Fourteen days post-stress sIgA concentrations of exam students were still significantly lower than control levels (P=0.004). No recovery was observable. At the same time exam students and controls did not differ in terms of self-reported stress and recovery. CONCLUSIONS: Psychological and immunological stress effects may be dissociated, the latter considerably exceeding the stress period. A closer look at the temporal dynamics of stress-induced immune alterations might increase our understanding of psychoimmuno relationships.

After-effects of stress on crevicular interleukin-1beta.

BACKGROUND: In a previous study, we found stress to increase crevicular interleukin-1beta (Il-1beta) secretion induced by supragingival plaque. While in that study, stress and plaque were presented concomitantly, we now wondered whether a consecutive presentation of these 2 factors would still exert stress effects. METHOD: 39 medical students participated in the study; 18 took part in a major exam while the remaining 21 served as controls. From the day after the last exam, students neglected oral hygiene in 2 antagonistic quadrants for 21 days (experimental gingivitis), while they maintained perfect hygiene at the remaining sites. Crevicular fluid samples were taken at days 0, 5, 8, 15, 18, and 21 of experimental gingivitis. RESULTS: A significant effect of pre-exposure to academic stress on crevicular Il-1beta concentration was found (area under the curve: p=0.042), the effect size, however, being smaller than in our previous study when stress and plaque were presented concomitantly. CONCLUSIONS: It is concluded that pre-exposure to stress may persistently alter the immunological effects of microbial challenge to the periodontium.

Immunological parameters in humans exposed to pesticides in the agricultural environment.

Immune parameters were examined in 224 sera of non-exposed controls and in 304 sera of pesticide applicators in the agricultural environment. In comparison to the control group pesticide applicators showed significant increased odds ratios for neopterin and soluble tumor necrosis factor receptor (sTNF RII) and a decreased odds ratio for immunoglobulin M. Obtained results indicate an enhanced macrophage activation and an impaired humoral defense. These alterations have been found to correlate with exposure duration in the group of pesticide applicators in agriculture. For subjects who worked in indoor pest control an inverse correlation for sTNF RII with exposure duration was obtained indicating impairment of cell mediated immune function. It can be concluded that exposure to pesticides in the agricultural environment may contribute to modulation of the immune system. Since immune modulating agents can potentially lead to adverse health consequences the involvement of immune biomarkers in pesticide-related health studies seems to be of considerable value for risk assessment studies.

Increase of crevicular interleukin 1beta under academic stress at experimental gingivitis sites and at sites of perfect oral hygiene.

This study analyses the effects of academic stress on crevicular interleukin-1beta(I1-1beta) both at experimental gingivitis sites and at sites of perfect oral hygiene. I1-1beta is thought to play a predominant role in periodontal tissue destruction. 13 medical students participating in a major medical exam (exam group) and 13 medical students not participating in any exam throughout the study period (control group) volunteered for the study. In a split-mouth-design, they refrained from any oral hygiene procedures in two opposite quadrants for 21 days (experimental gingivitis) while they maintained perfect hygiene levels at the remaining sites. Crevicular fluid was sampled for further I1-1beta analysis at teeth 5 and 6 of the upper jaw at days 1, 5, 8, 11, 14, 18 and 21 of the experimental gingivitis period. Exam students showed significantly higher I1-1beta levels than controls both at experimental gingivitis sites (area under the curve, exam group: 1240.64+/-140.07; control group: 697.61+/-111.30; p=0.004) and at sites of perfect oral hygiene (exam group: 290.42+/-63.19; control group: 143.98+/-42.71; p = 0.04). These results indicate that stress might affect periodontal health by increasing local I1-1beta levels especially when oral hygiene is neglected.

Soluble tumor necrosis factor receptor (sTNF RII) in sera of children and traffic-derived particulate air pollution.

Tumor necrosis factor receptor (sTNF RII) was determined in sera of 160 healthy schoolchildren of the city of Düsseldorf, Germany, living in areas with different traffic density. According to the frequency distribution a higher prevalence of children with increased sTNF RII values (> 3000 pg/ml) were found for a high traffic area as compared to a low traffic area. Based on sTNF RII values above the 75% percentile of children from the low traffic area, the group of children from the high traffic area revealed a significant increased odds ratio of 2.5. Concerning traffic-derived particulate air pollution an association between the concentration of fine particles (PM2.5) and sTNF RII serum levels could be observed for both areas. Furthermore, sTNF RII values gave a significant positive correlation with C3c, an activation product of the complement component C3. C3c has been shown to be a sensitive indicator of the non-specific humoral defence in response to air pollution. Therefore, the results suggest that traffic-derived fine particles may upon inhalation trigger immune modulation via the activation of macrophages and enhanced cytokine production.

Inverse social gradient of secondary immune response parameters in children.

BACKGROUND: In children, the prevalence of allergy increases with increasing socioeconomic status. If frequent immune response stimulation by infections protects against development of allergic diseases, then a social gradient in infections should exist. The aim of our study was to assess the relation between social class, immune parameters, and the prevalence of respiratory infections in children. METHODS: A cross-sectional survey examined children aged 5 to 14 years in 3 communities of Sachsen-Anhalt, Germany. Data of 1724 children were gathered by a parent-completed questionnaire and analyses of blood samples. Social class was defined by parental educational level. Immune parameters included serum immunoglobulin (Ig)G, IgA, and IgM; the C3c component of complement; and the total leukocyte count. The period prevalence of febrile colds and lifetime prevalences of physician-diagnosed bronchitis, tonsillitis, otitis media, and pneumonia were assessed from parents' reports. Adjusted odds ratios for the association between social class and belonging to the group of children with immune parameter levels in the upper 50th or 75th percentile or experiencing respiratory infections were calculated by logistic regression. RESULTS: Social class was inversely associated with secondary immune response parameters (IgG, IgA), whereas indicators of primary immune reactions and inflammation (IgM, C3c, leukocytes) were not related to social status. While an inverse social gradient was found for the period prevalence of febrile colds, the frequency of bronchitis, tonsillitis, and otitis media decreased with decreasing social class. CONCLUSIONS: Health inequalities exist in immune reactions and respiratory infections in children from different social classes. We hypothesize that in children from lower social classes, increased frequency of infections stimulated the secondary immune response and protected against more severe courses of respiratory infections.

Serum immunoglobulin level and skin prick test response.

OBJECTIVE: The relation of viral infections and allergic diseases is inconclusive. The objective of the analysis therefore was to examine the relation between immunoglobulin levels and sensitization to common allergens as measured by the skin prick test (SPT). METHODS: In a population-based study of 2,470 children, 2,188 skin prick tests, and 2,042 blood samples could be analyzed. RESULTS: At least one positive SPT was observed in 19.2% of the children. IgA und IgG levels did not show any association with SPT response. As expected, there was a sharp increase in the two highest quartile groups of IgE (p for trend <0.0001), while the prevalence of positive SPT continuously decreased with higher IgM levels (p for trend 0.002). This effect of IgM could be seen for all allergens examined. If an upper respiratory tract infection was reported one week prior to testing, the prevalence of a positive SPT was also reduced by nearly one half, however, this association was not significant. CONCLUSIONS: Since IgM has a half-life of approximately 5 days, the inverse association found between IgM and the prevalence of positive SPT seems to be a transient effect of a prior infection.

Immunological alterations in sera of persons living in areas with different air pollution.

The present study aimed to investigate immune parameters in sera of adult persons chronically exposed to different degrees of ambient air pollution. As related to air pollution derived from coal mining industry and coke plants, a significantly increased prevalence of cases with abnormally high serum levels of the immunoglobulins IgA and IgM as well as the complement component C3c was found as compared with a less polluted control area, indicating a higher stimulation of acute reactants in combination with a polyclonal immune response. These findings may be attributed to elevated concentrations of airborne particulates, suggesting that permanent exposure to increased levels of airborne particulates leads to chronic irritation of the airways in association with activation of the immune system, which may give rise to an enhanced risk for chronic airway diseases.

Influence of air pollution on humoral immune response.

To learn more about the effects of ambient air pollution on the human immune system, immunological parameters-16 serum proteins and circulating immune complexes--were determined for more than 500 women from the polluted area of Cologne, Germany, and a control area, Borken. The geometric mean values for immunoglobulins, complement components, haptoglobin, alpha 1-acid glycoprotein, alpha 1-antitrypsin, ceruloplasmin, alpha 2-macroglobulin, prealbumin, and transferrin were statistically significantly higher in Cologne than in Borken. No difference were found for C-reactive protein, rheumatoid factors, and anti-streptolysin O. For each of the parameters a logistic regression was fitted, thus controlling for the influence of a number of confounding factors. After controlling for possible confounders, the percentages of values above the norm for immunoglobulins, complement components, haptoglobin, and alpha-1-glycoprotein were statistically significantly higher in Cologne than in Broken. Important confounders included overweight, high blood pressure, acute cold, fever in the preceding week, and smoking. The biochemical mechanisms underlying the observed interarea differences in protein profiles are as yet unknown and should be the subject of further, nonepidemiological research.

[Antibodies to tetanus toxoid in children from areas with different heavy levels of air pollution]. / Tetanustoxoid-Antikörper bei Kindern aus Gebieten mit unterschiedlich starker Luftverunreinigung.

The aim of this study was to investigate the relationship between different levels of air pollution and IgG antibody titers against tetanus toxoid in sera of 6 year old children (n = 354). Additionally, other parameters of the humoral immune response (immunoglobulins G, A, M, total IgE, complement component C3c, C-reactive protein (CRP)) were analysed. The index areas were Leipzig, Magdeburg (Saxony/Saxe-Anhalt), and Duisburg, Dortmund (Ruhr region). The control areas were Osterburg and Borken. IgG antibodies against tetanus toxoid were measured by ELISA in sera of children vaccinated three times DPT in early childhood. The other humoral parameters were measured by nephelometry. In comparison to the control area Borken the sera of children living in the index areas Duisburg and Dortmund showed a lower antibody titer. There were no differences between the index areas (Leipzig, Magdeburg) and the control area Osterburg. It has to be taken into account that the choice of Osterburg as a control area is problematic because of the lack of data on air pollution. Statistically, there was no relationship between antibody titer against tetanus toxoid and the additionally measured parameters of the humoral immune response.

[The concentration of alpha-1-PI in the serum of 55-year-old women from regions with different levels of air pollution in North Rhine-Westphalia]. / Die Konzentration von Alpha-1-PI im Serum 55-jähriger Frauen aus Regionen mit unterschiedlicher Luftbelastung in NRW.

It has been shown that smoking leads to an increase in the serum level of alpha-1-proteinase inhibitor (API). The aim of this study was to examine whether there is an influence of air pollution on the serum level of API as well. Our survey was done on 781 women in the age of 55 years residing in areas differing in outdoor air pollution levels (SO2, NOx, particulate matter, heavy metals). Blood samples were taken for serum analysis. API and several other parameters of the specific and unspecific humoral immunity were measured using nephelometry. Information about respiratory health, active and passive smoking, type of heating and education were obtained by questionnaire. Statistical analysis was restricted to non-smokers (n-s). After adjusting for confounding variables (COPD, ETS, type of heating) we found a statistically significant (p. < 0.0001) difference between the index and the control area. One important function of API lies in the antagonism of the elastase from neutrophil granulocytes. Thus our results--which parallel those seen in smokers--may indicate an impact of environmental air pollution on the non-specific immunity of the bronchi, which are directly exposed to the pollutants. We therefore consider API as a good marker of biological effects in environmental epidemiology.

C3c concentrations in sera of persons living in areas with different levels of air pollution in Northrhine-Westphalia (Federal Republic of Germany).

A number of air pollutants is known to affect the immune system resulting in alterations of the complement activity in serum. We determined the levels of C3c, one of the activation products of the component C3, in serum samples obtained from various population groups living in areas with different levels of air pollution in Northrhine-Westphalia (FRG). The results show that the serum C3c levels tend to be increased in subjects living in areas with elevated levels of air pollution. By applying a linear regression model it can be demonstrated that a significant part of the variance of the C3c concentrations is explained by the residence area factor after making allowance for the effect of various confounders. The increase of the serum C3c concentrations appears to result from an increased activation of the complement component C3. The underlying mechanisms as well as the pathophysiological significance of these findings are unknown.

Immunopathological signs in mice treated with mercury compounds--I. Identification by the popliteal lymph node assay of responder and nonresponder strains.

In the present study we screened mice from 22 different inbred strains for potential differences in their immunological reaction to HgCl2. As a rapid screening test, we used the popliteal lymph node assay (PLNA). Mice were injected s.c. into one hind footpad with 3-60 micrograms of Hg2+, given as HgCl2 in phosphate-buffered saline (PBS); contralateral hindfeet remained uninjected. Control mice received PBS alone. On day 6 the weights of the draining and contralateral PLN were determined and the PLN index calculated. While we found linear dose-response curves in some strains, these curves had a different shape in others. Out of the total of 21 euthymic strains tested only strain DBA/2 (H-2d) proved to be a nonresponder to HgCl2; it remained a nonresponder over the whole dose range (3-180 micrograms Hg2+) and period of time (days 2-12) studied. The other H-2d strains tested, i.e. NZB, BALB/c and B10.D2/n, showed absent or low PLN responses only in the lower dose range (3-30 micrograms Hg2+). F1 hybrids of strain DBA/2 and the responder strain C57BL/6 gave an intermediate response. While C3H nu/nu mice failed to respond to HgCl2, C3H +/nu mice did. The weight increase of the draining PLN after HgCl2 injection was preceded in time by an increased 3H thymidine uptake by the PLN. Histologically, enlarged PLNs revealed increased cellularity in both the T-cell and the B-cell areas. When CH3HgCl, instead of HgCl2, was injected all three strains tested, including DBA/2, responded by PLN enlargement. We conclude that (1) HgCl2 is an immunostimulatory agent in mice in that it induces T-cell-dependent enlargement of the draining PLN upon local injection, (2) there are striking genetic differences between inbred strains of mice in the PLN response to HgCl2, but these differences are not paralleled by similar differences in the response to CH3HgCl, (3) responsiveness to HgCl2 appears to be inherited in a codominant fashion, and (4) there is suggestive evidence that the observed genetic differences are determined by both H-2 and non-H-2 genes.

[Demonstration of antibodies against tumor-associated antigens in the serum patients with bronchogenic carcinoma using anticomplement immunofluorescence on xenotransplants of human tumors]. / Nachweis von Antikörpern gegen tumorassoziierte Antigene in Seren von Patienten mit Bronchialkarzinom mit Hilfe der Anti-Komplement-Immunfluoreszenz auf Xenotransplantaten menschlicher Tumoren.

209 sera of tumor-bearing patients and 133 control sera were tested by anti-complement immunofluorescence (ACIF) on 2 xenotransplants of human bronchogenic cancer and on 2 xenotransplants of rectum carcinoma passaged in nu/nu mice. Testing of sera from patients with bronchogenic carcinoma resulted in a positive reaction with the xenotransplants of bronchogenic cancer in 48.5 to 58.5%, and sera of patients with digestive tract cancer in 6.6 to 16.1%. On xenotransplants of rectum carcinoma 73.2 to 78.1% of the sera from patients with bronchogenic carcinomas and 22.6 to 29.1% of the sera of patients with digestive tract cancer reacted positively. Control sera were positive dependent on the xenotransplants in 2.0 to 12.5%. These results indicate that there are antibodies in the sera of tumor-bearing patients against one or more non organ specific tumor-associated antigen(s) occurring in an elevated concentration in carcinomas of the digestive tract than in bronchogenic carcinomas. After absorption of the sera with homogenates of bronchogenic carcinoma and liver metastases of colon carcinoma the reaction was inhibited in the ACIF, reaching control values.

Environmental exposure to cadmium and renal function of elderly women living in cadmium-polluted areas of the Federal Republic of Germany.

An epidemiological study was performed to assess whether environmental pollution by cadmium as found in cadmium-polluted areas of the Federal Republic of Germany is associated with an increased prevalence of biological signs of kidney dysfunction in population groups non-occupationally exposed to heavy metals. The study was run in two industrial areas known to be highly contaminated by cadmium, lead and other heavy metals, viz. Stolberg and Duisburg. Düsseldorf was selected as a reference area. As a study population we selected 65- and 66-year-old women (n = 286) who had spent the major part of their lives in one of these areas. The average cadmium levels in blood (CdB) and urine (CdU) revealed significant differences in exposure to cadmium in the order Stolberg greater than Duisburg greater than Düsseldorf. Serum creatinine levels were, on average, significantly higher in the Stolberg group than in the Duisburg and Düsseldorf groups. However, with respect to the urinary excretion of low molecular weight proteins (beta 2-microglobulin, retinol-binding protein), albuminuria, total proteinuria, aminoaciduria, phosphaturia and some other biological findings, no significant differences between the study populations were noted. Similarly, the prevalence of clinically-confirmed hypertension as well as the relative frequency of hypertensive subjects (systolic greater than or equal to 160 and/or diastolic greater than or equal to 95 mm Hg) did not differ significantly among the three study groups. There was no exposure-response relationship between CdU and tubular proteinuria in the range of the CdU-levels found (0.1 to 5.2 micrograms/g creatinine). However, albuminuria tended to be increased at CdU levels greater than 2 micrograms/g creatinine.

[Are suppressor T-cells the primary target cells of lead immunotoxicity?]. / Sind Suppressor-T-Zellen die primären Zielzellen der immunotoxischen Wirkungen von Blei?

Studies were performed to investigate the effect of chronic low level lead exposure on the regulatory functions of T cells in the humoral immune response to sheep red blood cells (SRBC) in mice. Female mice were exposed to lead (as lead acetate) in the diet at 545 (group 1) and 2180 ppm (group 2) for 10 weeks. Lead exposure resulting in blood lead levels (PbB) of about 50 micrograms/100 g (group 1) produced a substantial increase of the number of IgG antibodies secreting spleen cells on days 3 and 4 after challenge. At the higher exposure level (group 2; PbB 60-80 micrograms/100 g) a suppression of the number of IgG plaque forming cells was observed. The IgM response was much smaller than the IgG response. Although differences between the group means were small, the results indicate that there also is an enhancement of the IgM response in the lower dosage group on days 3 and 4. In a second experiment the effect of in vivo lead exposure on antigenic competition was examined. Lead substantially reduced the effect of antigenic competition. Results of both experiments suggest that suppressor T cells rather than helper T cells may represent the primary target for lead. Throughout this study serum complement C3 levels were determined. Complement C3 levels tended to be reduced in the lead exposed groups before as well as after inocculation with SRBC.

The recognition of human bronchogenic carcinomas.

Xenotransplants of human carcinomas were tested for consistency of the analytical data of tumor markers over several passages in nude mice and nude rats. The binding properties of antibodies against tumor-associated antigens present in sera from tumor-bearing patients were tested with aid of the anticomplement immunofluorescence. The best binding capacity was found when sera from patients with bronchogenic carcinomas reacted on xenotransplants of the digestive tract (70%). Because of the low values for controls as well as for inflammatory diseases, this test may be applicable in the early recognition of lung cancer.

[Antibodies against tumor associated antigens of human bronchogenic carcinoma: demonstration by anti-complement immunofluorescence (author's transl)]. / Semiquantitative Bestimmung von Antikörpern gegen tumor-assoziierte Antigene in Seren von Bronchialkarzinomträgern mit Hilfe ker Anti-Komplement-Immunfluoroeszenz.

A method of anti-complement immunofluorescence is described for semiquantitative measurement of antibodies in 281 sera samples obtained from patients with bronchogenic carcinoma. Tests were performed on frozen sections of 17 human bronchogenic carcinoma. - 168 sera obtained from healthy persons were used as control. Tumor and control sera were also tested on frozen sections of 10 normal lungs. - The intensity of fluorescence was measured by incident light with the aid of a Leitz microscope photometer. In comparison to control sera the mean values of fluorescence intensity of the tested 281 tumor sera were significantly higher when frozen sections of bronchogenic carcinoma were used. - In order to allow for the different content of antigens in the bronchogenic carcinoma we have calculated the rations of the tested tumor and control sera on tumor and normal sections. - The percentage of positive results showed strong dependence on the histological type of the bronchogenic carcinoma used as frozen section and differed between 16,3 and 69,1%. The highest percentage of positive reactions resulted when tumor sera were tested on frozen sections of undifferentiated bronchogenic carcinoma. Besides that sera from patients suffering from small cell bronchogenic carcinoma gave more positive results than sera from patients with other bronchogenic carcinoma. - In 78,3% of the carcinoma were tested on frozen sections of undifferentiated bronchogenic carcinoma.