Renate Stiller-Winkler

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.

Serum immunoglobulin, complement C3, and salivary IgA levels in lead workers

Sera of 72 lead workers and of 53 reference subjects were examined for levels of immunoglobulins IgM, IgG, and IgA, and complement C3 by radial immunodiffusion. Salivary IgA levels were determined in 33 lead workers and 40 reference subjects. On the average the lead workers had lower serum complement C3 and immunoglobulin levels, as well as lower salivary IgA levels, than the reference subjects. A significant negative correlation was found between blood lead concentrations (PbB) and the serum levels of complement C3 and IgG in the group of lead workers, as well as in the total population examined. However, a significant positive correlation was observed between PbB and serum IgA in the group of lead workers. The results obtained in this study are discussed in relation to numerous reports in the literature showing that lead exerts adverse effects on the immune system in animals.

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

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.

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.

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.

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.

Prevalence of respiratory symptoms in school children and salivary IgA – an epidemiological study in a rural area of Northrhine-Westphalia, Germany

An elevated frequency of wheezing was found in school children in a rural area of Northrhine-Westphalia, Germany (Duhme and Keil, Institut für Epidemiologie und Sozialmedizin, Universität Münster, Münster, Germany 1997). In this study the prevalence of wheezing was reinvestigated by including main influencing factors. A cross-sectional survey was performed in all school children visiting school classes 1, 2 and 7, 8 (n = 1161). Two corresponding questionnaires were used: a parental questionnaire and a questionnaire for self-completion by the children aged 12-15. The latter included the ISAAC video questionnaire. The levels of immunoglobulins A, G and M were determined in 995 saliva samples. Testing of lung function (whole body plethysmography before and after physical exercise) was performed in children with and without parent-reported wheezing in the last 12 months (n = 377). Response rate (questionnaire: 93%) and participation rates (saliva samples: 86%, lung function tests: 93%) were high. Our study confirmed higher prevalence of asthmatic symptoms in children aged 6-8 in Ochtrup (13.2%) compared to children of the same age in Muenster (8.5% (Duhme et al., Eur. Respir. J. 11, 840-847, 1998)). However, in the age group 12-15 years the prevalence was significantly lower in Ochtrup (9.8%), when compared to the former investigation and in comparison to Muenster (former survey: 17.9%; Muenster: 13.1%). Prevalence of wheezing was consistently higher in families with atopic disease. Additionally, history of respiratory disease, premature birth and presence of pets during 1st year of life showed a positive association with prevalence of wheezing. Mean salivary IgA levels were 61.4 (SD (standard deviation) 35.1, median: 53.7) mg/l in children aged 6-8 years and 83.4 (SD 39.0, median: 76.3) mg/l in children aged 12-15 years. No significant association between salivary immunoglobulins and wheezing was detected.

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.