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26 Studies --- PCBs & Immune
Deficiency Disease
This is not a complete list of all studies on this topic.
For more studies, visit the TOXNET
database operated by the National Library of Medicine (the source of these
abstracts).
Study #1
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background levels of PCB/dioxin exposure influences the human
fetal and neonatal immune system.
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increase in the total number of T cells
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increase in the number of TcR gamma delta+ T cells
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increased in the number of CD8+ (cytotoxic), TcR alpha beta+,
and TcR gamma delta+ T cells
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lower monocyte and granulocyte counts
-
no relationship between pre- and postnatal PCB/dioxin exposure
and upper or lower respiratory tract symptoms or humoral antibody production
-
study examined only 4 types of PCBs (118,138,153 and 180)
for prenatal tests
-
study examined only 8 types of dioxin-like PCBs along with
17 types of dioxin for tests after birth
Immunologic effects of pre- and postnatal polychlorinated
biphenyl (PCB)/dioxin exposure in Dutch infants from birth to 18 mo of
age are explored. The total study group consisted of 207 healthy mother-infant
pairs, of which 105 infants were breast-fed and 102 children were bottle-fed.
Prenatal PCB exposure was estimated by the PCB sum (PCB congeners 118,
138, 153, and 180) in maternal blood and the total toxic equivalent (TEQ)
level in human milk (17 dioxin and 8 dioxin-like PCB congeners). Postnatal
PCB/dioxin exposure was calculated as a product of the total TEQ level
in human milk multiplied by the weeks of breast-feeding. The number of
periods with rhinitis, bronchitis, tonsillitis, and otitis during the first
18 mo of life was used as an estimate of the health status of the infants.
Humoral immunity was measured at 18 mo of age by detecting antibody levels
to mumps, measles, and rubella. White blood cell counts (monocytes, granulocytes,
and lymphocytes) and immunologic marker analyses CD4+ T-lymphocytes, CD8+
T-lymphocytes, activated T-lymphocytes (HLA-DR+CD3+), as well as T cell
receptor (TcR) alpha beta+, TcR gamma delta+, CD4+CD45RA+ and CD4+CD45RO+
T-lymphocytes, B-lymphocytes (CD19+ and/or CD20+) and NK cells (CD16+ and/or
CD56+/CD3-) in cord blood and venous blood at 3 and 18 mo of age were assessed
in a subgroup of 55 infants. There was no relationship between pre-
and postnatal PCB/dioxin exposure and upper or lower respiratory tract
symptoms or humoral antibody production. A higher prenatal PCB/dioxin
exposure was associated with an increase in the number of TcR gamma
delta+ T cells at birth and with an increase in the total number
of T cells and the number of CD8+ (cytotoxic), TcR alpha beta+,
and TcR gamma delta+ T cells at 18 mo of age. A higher prenatal as
well as postnatal PCB/dioxin exposure was associated with lower monocyte
and granulocyte counts at 3 mo of age. In conclusion, our study suggests
that background levels of PCB/dioxin exposure influences the human fetal
and neonatal immune system. (Weisglas-Kuperus et al, 1995)
Study #2
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PCBs are linked to long-term immune effects (decades after
poisoning)
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autoantibodies in patients with Yusho PCB poisoning are frequent
--- (which may make them vulnerable to autoimmune disorders)
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45.6% for antinuclear antibody, 12.7% for rheumatoid (arthritis)
factor and 11.1% for thyroglobulin antibody
-
serum levels of immunoglobulin A(IgA), immunoglobulin G(IgG)
and immunoglobulin M(IgM) were elevated in 12.7%, 24.1% and 8.9%
-
thyroglobulinantibody was detected in 19.5% of people with
higher PCB exposures
-
mean absolute density of CD4 positive lymphocytes was higher
-
exposure to background levels of chlorinated dioxins and
related chemicals through breast milk may cause some immunologic disorder
-
chlorinated dioxins and related chemicals from the breast
milk correlated negatively with the percentages of CD8 positive lymphocytes
To evaluate chronic immune effects of endocrine disruptors,
serum autoantibodies and immunoglobulin concentrations were studied in
patients with Yusho. Autoantibodies were present in some patients of Yusho;
45.6%
for antinuclear antibody, 12.7% for rheumatoid factor and
11.1%
for thyroglobulin antibody. LE factor was not detected. Serum levels
of immunoglobulin A(IgA), immunoglobulin G(IgG) and immunoglobulin M(IgM)
were elevated in 12.7%, 24.1% and 8.9%, respectively. Thyroglobulinantibody
was detected in 19.5% of Yusho patients with high PCB concentration(higher
than 3.0 ppb),and in only 2.5% of patients with low PCB concentration (lower
than 2.9 ppb). Furthermore, the mean absolute density of CD4 positive
lymphocytes was higher in patients with high PCB concentration than
in patients with low PCB concentration. We conclude that autoantibodies
in patients with Yusho are frequent, and it may be associated with
the increase of helper/inducer T cells. Effects of lactational exposure
to chlorinated dioxins and related chemicals on lymphocyte subpopulations
in Japanese babies were also studied. Estimated total TEQ intakes of chlorinated
dioxins and related chemicals from the breast milk correlated negatively
with the percentages of CD8 positive lymphocytes. It is showed that
exposure
to background levels of chlorinated dioxins and related chemicals through
breast milk may cause some immunologic disorder. (Tsuji,2000)
Study #3
-
increased levels of dioxins and related compounds (PCBs)
correlate with negative changes in lymphocyte subpopulations and CD4+/CD8+
biomarkers
-
dioxin and related compounds may be related to immunopathy,
such as atopic dermatitis
-
exposures occurred at background levels
We investigated PCDDs and related compounds in the blood
of young Japanese women, approximately 20 years of age, who had not yet
had children, and discussed how the TEQ level of PCDDs and related compounds
in their blood may affect the next generation. Means of total TEQ levels
were 0.063 pg/g for whole blood basis and 21 pg/g for lipid basis. TEQ
of PCDDs, PCDFs and coplanar PCBs accounted for about 43, 34 and 23% of
the total TEQ in the whole blood basis, respectively. In the lipid basis,
their values were about 44, 34 and 22%, respectively. Previously, we investigated
PCDDs and related compounds levels in mother's breast milk, lymphocyte
subpopulation and thyroid function of their children, and found negative
correlations between the TEQ level of PCDDs and related compounds and CD4+/CD8+,
and/or the TEQ level of PCDDs and related compounds and the T4 level in
36 mothers and children. Of these cases, the average age was approximately
28 years. PCDDs and related compounds may be related to immunopathy, such
as atopic dermatitis. The effects of PCDDs and related compounds on babies
of young Japanese women are important and must be further evaluated. (Iida
et al, 1999)
Study #4
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PCB poisoned children suffer increased rates of bronchitis,
respiratory tract and ear infections, and influenza attacks
-
suppressed immunity was not demonstrated with serum immunologic
market analyses
-
immune functional tests may be necessary to detect changes
(such as delayed hypersensitive skin reaction, in vitro lymphocyte proliferation,
and antibody synthesis following immunization)
The immunologic effects of in utero exposure to polychlorinated
biphenyls (PCBs)/polychlorinated dibenzofurans (PCDFs) were evaluated in
the Yucheng children in this study. The study subjects consisted of 105
Yucheng children and 101 control children. The Yucheng children were born,
between July 1978 and June 1987, to women who had exposed to high dose
of PCBs/PCDFs through consumption of contaminated rice bran oil in 1978-1979.
These children had been reported to have higher frequencies of bronchitis
than their controls in the first six months of life, and higher frequencies
of respiratory tract and ear infection in a 6-year follow-up. The low
resistance of the Yucheng children to infection suggested that their immune
function was suppressed by the PCBs/PCDFs they had exposed to in utero.
In the summer and fall of 1995, a thorough physical examination and blood
draw were performed on the study children. The Yucheng children were reported
by their parents to have higher frequencies of influenza attacks
than the control children during the six months prior to the examination.
The frequencies of other symptoms were similar between the two groups.
The serum levels of various immunoglobulins were similar between the two
groups. Fifty-one serum samples, 29 of Yucheng and 22 of control children,
were available for cell-mediated immunologic analysis. The percentages
of various T cell markers, CD3, CD4, and CD8, and B cell and NK cell markers
were not different between the Yucheng and the control children. No dose-response
relationship was found between 27 Yucheng children's serum PCB/PCDF levels
and any of their immunologic markers. WE concluded that 16 years after
the Yucheng incident, Yucheng children exposed to high dose of PCBs/PCDFs
in utero did not show, with the serum immunologic marker analyses, suppressed
immunity when compared to their controls. To explain the consistent
higher frequencies of upper respiratory tract infection in the Yucheng
children, immune functional tests such as delayed hypersensitive skin
reaction, in vitro lymphocyte proliferation, and antibody synthesis following
immunization may be necessary. (Yu et al, 1998)
Study #5
-
impaired immune functioning may result in neuropsychological
impairment (brain damage)
-
study involved dioxin and PCB poisoned children (certain
PCBs are dioxin-like)
Exposure to 2,3,7,8-TCDD as well as related dioxins, polychlorinated
biphenyls and dibenzofurans, in utero and postnatally have previously
been related to impaired mental functioning in later infant and child mental
development. Fourteen children were selected from families exposed to TCDD
in Times Beach, Missouri between 1971 and 1983. Seven girls (mean age =
11.28) and 7 boys (mean age = 10.71) born between 1977 and 1983 to mothers
who resided in the TCDD-contaminated environment during and subsequent
to pregnancy were selected for study. The sample had no history of head
injury. The group revealed an atypical distribution of medical complications.
Immunoassay analyses noted abnormal immunological functioning. Neurometric
quantitative EEG and P300 evoked potential tests were used to evaluate
neurophysiological functional status. T-tests indicated that the frontal
regions not only show more statistically deviant measures than other cortical
regions but also the absolute mean values of these deviations from normal
are greater than other regions. Of interest are the findings of a sex difference
in the absolute deviation from normal for mean values in the cortical regions.
Neuropsychological tests were conducted on this same group of children.
While the group appeared to be functioning within the broad definition
of normal on intelligence testing, males showed more impairment on visual-motor
tasks while females exhibited more impairment of problem solving skills
in the visual modality. All children exhibited problems with attention.
Despite the diversity of geographic locations and rearing environments
of these children, the one common factor linking their problems is their
exposure to 2,3,7,8-TCDD. Collectively, these findings suggest that impaired
immune functioning as a result of exposure to 2,3,7,8-TCDD may contribute
to the maldevelopment of neurochemical systems with resultant neuropsychological
impairment. Sex differences in these findings may suggest neuroendocrine
interactions in these findings. (Cantor et al, 1996)
Study #6
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non-Hodgkin’s lymphoma risk increases in humans with immune
deficiencies or autoimmune disorders
-
non-Hodgkin’s lymphoma has been associated with PCB exposure
-
non-Hodgkin’s lymphoma may result from a combination of chemical
immunosuppression and virus infection
In epidemiologic studies, non-Hodgkin's lymphoma (NHL) has
been associated with exposure to chemicals such as phenoxyacetic acids;
chlorophenols; dioxins; organic solvents including benzene, polychlorinated
biphenyls, chlordanes; and immunosuppressive drugs. Experimental evidence
and clinical observations indicate that these chemicals may impair the
immune
system. The risk is increased for NHL in persons with acquired and
congenital immune deficiency as well as autoimmune disorders. Also,
certain viruses have been suggested to be of etiologic significance for
NHL. In some cases of NHL the common mechanism for all these agents and
conditions may be immunosuppression, possibly in combination with
viruses. (Hardell et al, 1998)
Study #7
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PCBs are associated with non-Hodgkin’s lymphoma (NHL), possibly
due to immune system impairment
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eliminating PCB exposures could help prevent NHL
Immunosuppression, possibly in combination with viruses,
could be a main etiologic mechanism for non-Hodgkin's lymphoma (NHL). Chemicals
such as phenoxyacetic acids, chlorophenols, dioxins, organic solvents,
polychlorinated
biphenyls, chlordane, and immunosuppressive drugs have been associated
with this disease. Also UV light and blood transfusion have been postulated
to be risk factors. Conclusive evidence of a causal association with NHL
is not established for all of these exposures, but experimental evidence
and clinical observations indicate that all these exposures have in common
that they may impair the immune system. Furthermore, acquired and
congenital immune deficiency as well as autoimmune disorders increase the
risk for NHL. In view of currently available evidence, the first priority
for reducing morbidity due to NHL might be to take action against adverse
chemical exposures as a measure that is more easily achievable than any
other kind of prevention. (Hardell & Axelson, 1998)
Study #8
-
organochlorines have been reported to adversely affect the
human immune system, reducing defenses against cancer
-
organochlorine exposure has been shown to increase risk of
non-Hodgkin’s lymphoma
-
immune damage combined with estrogenic qualities (as with
PCBs) have been linked to breast cancer
The association between increased risk of nonHodgkin's lymphoma
(NHL) or breast cancer and exposure to organochlorine compounds (OCs) was
reviewed. Several organochlorines have been reported to adversely affect
the human immune system, providing a mechanism whereby immunological defense
against early cancer stages and immune cells themselves may be influenced
by this class of chemicals. In addition, some of these compounds have been
reported to have estrogenic effects contributing additional evidence for
their role in the induction of breast cancer. Epidemiological studies on
the risk of NHL from OC exposure have consistently demonstrated an increased
risk for NHL associated with exposure to pesticides, particularly herbicides.
Studies of breast cancer risk from OC exposure have shown increased levels
of polychlorinated biphenyl, DDT (50293) and DDE (3547044) in breast
tissue samples obtained from breast cancer cases. Methodological issues
complicating the interpretation of such studies were discussed. The author
presents several recommendations regarding the control and use of OCs.
(Hoffmann, 1996)
Study #9
-
prenatal organochlorine exposure could be a risk factor for
increased ear infections in infants
We investigated whether organochlorine exposure is associated
with the incidence of infectious diseases in Inuit infants from Nunavik
(Arctic Quebec, Canada). We compiled the number of infectious disease episodes
during the first year of life for 98 breast-fed and 73 bottle-fed infants.
Concentrations of organochlorines were measured in early breast milk samples
and used as surrogates to prenatal exposure levels. Immune system parameters
were determined in venous blood samples collected from infants at 3, 7,
and 12 months of age. Otitis media was the most frequent disease, with
80. 0% of breast-fed and 81.3% of bottle-fed infants experiencing at least
one episode during the first year of life. During the second follow-up
period, the risk of otitis media increased with prenatal exposure to p,p'-DDE,
hexachlorobenzene, and dieldrin. The relative risk (RR) for 4- to 7-month-old
infants in the highest tertile of p, p'-DDE exposure as compared to infants
in the lowest tertile was 1. 87 [95% confidence interval (CI), 1.07-3.26].
The RR of otitis media over the entire first year of life also increased
with prenatal exposure to p,p'-DDE (RR, 1.52; CI, 1.05-2.22) and hexachlorobenzene
(RR, 1.49; CI, 1.10-2.03). Furthermore, the RR of recurrent otitis media
( [Greater/equal to] 3 episodes) increased with prenatal exposure to these
compounds. No clinically relevant differences were noted between breast-fed
and bottle-fed infants with regard to immunologic parameters, and prenatal
organochlorine exposure was not associated with immunologic parameters.
We conclude that prenatal organochlorine exposure could be a risk factor
for acute otitis media in Inuit infants. (Dewailly et al, 2000)
Study #10
-
higher incidence of bacterial infections in babies of PCB
exposed mothers
-
the immune system is a potential target for the immunotoxic
effects of PCBs
Polychlorinated biphenyls (PCBs) are among the most widespread
environmental pollutants and a prominent contaminant of the Great Lakes
basin. Due to their resistance to biodegradation and lipophilic properties,
PCBs bioaccumulate in fish tissues and in fish-eating humans. PCBs are
also known to cross the placenta and to be excreted into the mother's milk,
thus predisposing the infant to potentially adverse health effects. For
example, a higher incidence of bacterial infections was reported
for breast-fed infants born to mothers who consumed large amounts of Great
Lakes fish compared to the incidence in control infants whose mothers ingested
low amounts of fish. While data regarding the PCB-induced immunotoxic effects
in humans are scarce, data derived from the use of experimental animals,
including nonhuman primates, indicate that the immune system is a potential
target for the immunotoxic effects of PCBs. Such studies have used
the commercially available PCB mixtures alone. However, PCBs have the po
(incomplete abstract) (Tryphonas, 1995)
Study #11
-
increased respiratory symptoms correlated with PCB exposure
in poisoned humans, along with viral or bacterial infections
-
immunoglobulin-A and immunoglobulin-M levels were decreased,
while immunoglobulin-G level was increased
Respiratory involvement and immune status was studied and
followed up for 14 years in 401 patients with polychlorinated-biphenyl
(1336363) (PCB) poisoning caused by ingestion of contaminated edible rice-bran-oil.
Respiratory
symptoms correlated with PCB levels in blood and were often exacerbated
by viral or bacterial infection. Symptoms improved gradually but
remained after 14 years. Study and follow up included assessment of subjective
symptoms, chest x-rays, pulmonary function tests, sputum microbiology,
and measurement of immunoglobulin and PCB levels in serum and sputum. Pulmonary
function and immunological status observed in February and March of 1983
(11 year follow up) were reported. Approximately 1 year after onset of
disease, half of the patients complained of expectoration; these patients
had high blood PCB concentrations. In some patients, wheezes without radiological,
physiological, or immunological evidence of bronchial asthma or pulmonary
emphysema were observed. For 5 years after onset, respiratory symptoms
persisted in most patients; in patients with high blood PCB levels, signs
of chronically infected airways were observed. PCB levels in blood
changed little during the observation period. Pulmonary function was tested
in 12 nonsmoking patients; in eight, inspiratory and expiratory rhonchi
were audible at all times in 1970 and 1974 (2 to 6 years after disease
onset). In 1983, slight improvement was observed and no audible rhonchi
were noted. Immunoglobulin-A and immunoglobulin-M levels were decreased,
while immunoglobulin-G level was increased in 1970. In 1972, these
immunoglobulins were normal except in three patients. In Sprague-Dawley-rats
fed polychlorinated dibenzofurans (PCDFs) (0.25 milligrams three times
per week for 1 or 2 weeks), pathologic changes in lungs and thymus
were observed, including necrosis of Clara cells, mild pulmonary edema,
and thymic atrophy, with similar but milder effects noted for PCBs.
The authors conclude that respiratory involvement in patients with PCB
and PCDF poisoning is located mainly in small airways and is due primarily
to PCDFs. [Note: PCBs and furans are generally found together.] (Nakanishi
et al, 1995)
Study #12
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PCB caused suppression of cellular immunity such as the delayed-type
skin response to streptokinase and streptodornase
Polychlorinated biphenyl (PCB) poisoning causes many physiological
abnormalities including immune suppression. Cellular immunity was
studied in 30 PCB-poisoned patients and 50 normal human subjects. PCB poisoning
caused suppression of cellular immunity such as the delayed-type skin response
to streptokinase and streptodornase. The suppression of cellular immunity
was correlated with the severity of the disease. Thus evaluation of the
immune function may be helpful for the diagnosis of PCB poisoning. (Chang
et al, 1982)
Study #13
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changes of lymphocyte subpopulations may be responsible for
immune deficiency due to PCBs
-
percentages of total T cells, active T cells and Tmu cells
decreased
-
decreased concentrations of IgA and IgM but not that of IgG
The concentration of serum Ig and the distribution of different
lymphocyte subpopulations were studied in peripheral blood samples obtained
from 30 human subjects exposed to PCB (polychlorinated biphenyl) and from
23 normal healthy subjects. PCB caused decreased concentrations of IgA
and IgM but not that of IgG. By using different rosette techniques to enumerate
the percentages of lymphocyte subpopulations, the percentages of total
T cells, active T cells and Tmu cells decreased, while the percentages
of B cells and Tgamma cells were not affected. Changes of lymphocyte subpopulations
may be responsible for the reported immune deficiency associated with PCB
exposure. (Chang et al, 1981)
Study #14
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background levels of organochlorine compounds through the
breast milk influences the human neonatal immune system
-
ratios of CD4+ to CD8+ T cells showed significant increasing
tendency correlated with organochlorine exposure
Effects of postnatal exposure to polychlorinated dibenzo-p-dioxins
(PCDDs), polychlorinated dibenzofurans (PCDFs) and coplanar polychlorinated
biphenyls (Co-PCBs) on lymphocyte subpopulations were investigated
in the peripheral blood of 36 breast-fed Japanese babies. As a result,
estimated total intakes of these chemicals in toxic equivalent quantity
(TEQ) converted into 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD)
equivalents from the breast milk positively and negatively correlated
with the respective percentages of CD4+ and CD8+ lymphocytes in the
blood of breast-fed babies. Consequently, the ratios of CD4+ to CD8+
T cells showed significant increasing tendency with the estimated total
TEQ intakes. Therefore, our study suggests that exposure to background
levels of the highly toxic organochlorine compounds through the breast
milk influences the human neonatal immune system. (Nagayama et al,
1998)
Study #15
-
decreased concentration of IgM and IgA but not of IgG
-
decreased percentage of total T-cells, active T-cells, and
helper T-cells
-
normal percentage of B-cells and suppressor T-cells
-
suppression of delayed type response to recalling antigens
-
enhancement of lymphocyte spontaneous proliferation
An outbreak of poisoning caused by ingestion of rice bran
oil which was accidentally contaminated with polychlorinated biphenyls
(PCBs) broke out in Taiwan in February 1979. Diagnosis, management,
and follow-up of the patients were performed at special clinics, and subjective
symptoms and cutaneous changes such as peculiar acneform eruptions and
pigmentation were recorded. The patients were divided into six age groups
of both essex, and the body surface of the patients was divided into 12
sections according to the nature of skin. The prevalence of each type of
cutaneous change was proved statistically by the chi-square test. The examination
of the immune system function in the patients at 1 year revealed: decreased
concentration of IgM and IgA but not of IgG; decreased percentage of total
T-cells, active T-cells, and helper T-cells, normal percentage of B-cells
and suppressor T-cells; suppression of delayed type response to recalling
antigens; enhancement of lymphocyte spontaneous proliferation; and
(incomplete abstract) (Yu et al, 1985)
Study #16
-
significantly lower PHA and ConA lymphocyte stimulation values
-
release of soluble CD23 (Fc epsilon RII) was higher
-
thrombocyte aggregation, serotonin release and 12-HETE formation
The study investigates the relation between strains on humans
due to certain chlorinated substances and changes in the immune system.
Immunological parameters were analyzed by testing a group of persons (persons
exposed to wood preservatives and PCB). In vitro tests were made to assess
the effects of polychlorinated biphenyl with regard to the release of mediators
of inflammation (chemoluminescence, leukotrienes, histamine, serotonin
12-HETE), cellular signal transduction (G proteins, proteinkinase C) and
lymphocyte parameters (CD23-Fc epsilon RII, CD25; lg synthesis). Compared
with untreated persons and the PCP test group PCB-exposed test persons
show significantly lower PHA and ConA lymphocyte stimulation values.The
release of soluble CD23 (Fc epsilon RII) was higher in exposed than
in non-exposed persons. Thrombocyte aggregation, serotonin release and
12-HETE formation furnish evidence of the fact that polychlorinated
biphenyls may induce and modulate cellular answers as a function of 1)
the (incomplete abstract) (Anonymous, Germany, 1993)
Study #17
-
weekly intake of fatty fish correlated negatively with proportions
of natural killer (NK) cells
-
significant negative correlations between numbers of NK cells
and blood levels of PCB 126
Consumption of fatty fish species, like salmon and herring,
from the Baltic Sea is an important source of human exposure to persistent
organochlorine compounds, e.g. polychlorinated dioxins (PCDDs), dibenzofurans
(PCDFs) and biphenyls (PCBs). Many of these compounds show immunotoxic
and
hepatotoxic effects in animals. We have now studied immunological competence,
including lymphocyte subsets, in 23 males with a high consumption of fish
from the Baltic Sea and in a control group of 20 males with virtually no
fish consumption. The high consumers had lower proportions and numbers
of natural killer (NK) cells, identified by the CD 56 marker, in peripheral
blood than the non-consumers. Weekly intake of fatty fish correlated
negatively with proportions of NK cells (rs = -0.32, P = 0.04). There
were also, in a subsample of 11 subjects, significant negative correlations
between numbers of NK cells and blood levels of a toxic non-ortho-PCB congener
(IUPAC 126; rs = -0.68, P = 0.02) and a mono-ortho congener (incomplete
abstract) (Svensson et al, 1994)
Study #18
-
secretory immunoglobulin A is strongly affected
-
increased readiness for allergic respiratory disease, through
the proof of hyperreactive mucous membranes
In the outskirts of Cairo, some 40,000 people live on garbage
dumps. These people form a closed population whose socio-economic problems
are identical. The pollutants are evenly distributed. Up to 30% of the
garbage on the polluted area, which cannot be recycled, is burned, resulting
in a high concentration of pollutants in the environment. The concentrations
of heavy metals, dioxins/furans, PCB, PAH in dust deposit and soil
were measured as well as the air pollutants SO2, HCl and CO. It was shown
that while the systemic immune system is only affected to a very small
degree, secretory immunoglobulin A is strongly affected by the emissions.
It could be demonstrated also an increased readiness for allergic respiratory
disease, through the proof of hyperreactive mucous membranes. In the
polluted area, 58% of the examined children were affected, whereas in the
control area only 22% displayed a hyperreactive mucous membrane. Also the
concentration of NANA (N-acetyl-N-neuraminic acid) in the serum, as a un
(incomplete abstract) (Marth et al, 1995)
Study #19
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PCB 104 induced DNR fragmentation and killed human monocytic
cells (parts of the immune system) through an unknown mechanism independent
of the arylhydrocarbon (Ah) receptor
-
PCB 104 decreased cell viability and induced cellular morphologic
features characteristic of cell death such as chromatin aggregation and
apoptotic bodies
-
PCB 126 (a dioxin-like PCB) did not kill monocytes, but potently
induced CYP 1A1 in human hepatoma Hep G2 cells
Polychlorinated biphenyls (PCBs) are a group of persistent
and widely dispersed environmental pollutants, some of which may be immunotoxic.
In the present study, we investigated the effect of PCBs on immune system
by assessing apoptotic cell death in human monocytic U937 cells. Among
the various congeners tested, 2,2',4,6, 6'-pentachlorobiphenyl (PeCB),
a highly ortho-substituted congener, specifically induced DNA fragmentation,
a hallmark of apoptosis, while the other examined di-, tri-, tetra-, and
pentachlorobiphenyls did not. To further study the 2,2',4,6,6'-PeCB-induced
cell death, various features of apoptosis were examined. 2,2',4,6,6'-PeCB
caused a decrease in cell viability and induced cellular morphologic
features characteristic of apoptosis such as chromatin aggregation and
apoptotic bodies. In addition, caspase-3, an executioner of apoptosis,
was activated and its substrate, poly(ADP-ribose) polymerase (PARP), was
cleaved during 2,2',4,6,6'-PeCB-induced apoptosis. In contrast, 3,3',4,4',5-PeCB,
a congener of coplanar structure, as well as 2,3,7,8-TCDD did not induce
apoptosis in these human monocytic cells, although they potently induced
CYP 1A1 in human hepatoma Hep G2 cells. Taken together, the data indicate
that 2,2',4,6,6'-PeCB induces apoptosis in human monocytic cells through
a mechanism that is independent of the arylhydrocarbon receptor. This
suggests a possibly separate mechanism by which PCBs cause immunosuppression.
(Shin et al, 2000)
Study #20
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thymic atrophy
-
immunosuppression
-
reduced thymocytes
-
study used PCB 77
The environmental pollutant 3,3',4,4'-tetrachlorobiphenyl
(TCB) leads to thymic atrophy and immunosuppression, the former possibly
causing the latter. TCB binds to the cytosolic aryl-hydrocarbon receptor
(AhR) and transforms it into a DNA-binding state. The development of fetal
thymocytes is severely affected by TCB and other AhR-binding xenobiotics,
leading to a skewed pattern of thymocyte maturation stages. Murine thymocyte
proliferation after exposure to TCB was studied in fetal thymus organ culture
(FTOC). C57BL/6 fetus thymic lobes from day 15 of gestation were explanted
and grown for 2, 4, 6, and 8 days in organ culture in the presence or absence
of 3.3 microM TCB. Subsets of thymocytes were defined by CD4 and CD8 surface
markers, and their cell cycle was analysed by DNA staining with 7-amino-actinomycin
D (7-AAD). Exposure of fetal thymi in vitro to 3.3 microM TCB significantly
reduced the total number of thymocytes, and fewer thymocytes were in S/G2M
phase. The inhibition of cell proliferation induced by TCB treatment affected
mainly the CD4-CD8- (double-negative, DN) and CD4-CD8+ (single-positive,
SP) subsets, and these inhibition appeared mainly in more immature thymocytes,
i.e. DNCD3- and CD8+CD3- subpopulations, whereas no effect of TCB on CD4+CD8+
(double-positive, DP) cell proliferative activity was observed. Analysis
of the relation of cell proliferation and development of subsets in differentiating
fetal thymocytes suggests that TCB enhanced thymocyte differentiation into
mature CD8+ cells. (Lai et al, 1994)
Study #21
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PCBs are immunotoxic
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tests have been created to selectively identify and quantify
PCBs 77, 126 and 169
Polychlorinated biphenyls (PCBs) are ubiquitous environmental
pollutants with diverse toxic, teratogenic, reproductive, immunotoxic,
and tumorigenic effects. Three of the least abundant of the 209 PCB isomers
(congeners) are the most toxic and most difficult to quantify. These are
3,4,3',4'-tetrachlorobiphenyl, 3,4,3',4',5'-pentachlorobiphenyl, and 3,4,5,3',4',5'-hexachlorobiphenyl
(IU-PAC No. 77, 126, and 169, respectively). An immunizing hapten was designed
to retain the 3,4,3',4' chlorine-substitution pattern and coplanarity characteristic
of these toxic congeners. The optimal competitors for immunoassay were
weaker binding distinctive single-ring fragments of the PCBs. A monoclonal
antibody designated S2B1 was derived and used in direct (antibody-capture)
competitive enzyme immunoassays (EIAs). The EIAs are highly specific for
non-ortho-substituted congeners and do not recognize the more prevalent
but much less toxic noncoplanar PCB congeners or 2,3,7,8-tetrachlorodibenzo-p-dioxin,
2,3,7,8-tetrachlorodibenzofuran, or dichlorobenzenes. Hapten and competitor
design for this assay suggests a basis for development of sensitive EIAs
for other classes of PCB congeners. (Chiu et al, 1995)
Study #22
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it should be possible to develop dioxin Toxic Euivalency
Factors (TEFs) for PCBs causing immune system damage
1. The methods used to evaluate the toxicological effects
of PCBs in animals have been reviewed. 2. The data show that Toxic Equivalency
Factors (TEFs) could be developed to assess the potential toxicity of PCB
mixtures for certain specific target organ effects (such as the liver and
immune system) but would be inappropriate for other effects (e.g. thyroid
function and neurochemical effects). More data on a wider range of individual
PCB congeners and a method for systematically balancing toxicodynamic and
toxicokinetic data are required before the TEF approach can be fully evaluated.
3. With the exception of the teratogenic effects seen in mice and the anti-oestrogenic
effects reported in in vitro studies, there are insufficient data on individual
PCB congeners to evaluate the structure-activity relationships for the
effects of PCBs on reproduction. The data also show that individual PCBs
may have opposing effects on a particular aspect of reproduction (for example
individual PCB congeners may have either oestrogenic or anti-oestrogenic
effects). Studies with individual PCB congeners have shown both enhancement
and antagonism of the teratogenic effects of 2, 3, 7, 8-tetrachloro dibenzo-p-dioxin
(TCDD) in the mouse. It is not possible to use TEFs to evaluate the reproductive
effects of PCBs. 4. The mechanism(s) responsible for the effects of PCBs
on postnatal neurobehavioural development in rodents and monkeys have not
been elucidated. At least two groups of PCBs which might be responsible
for the observed effects have been identified in this review, one affecting
the dopaminergic system and the other group affecting thyroid hormone levels.
Considerably more research would be required before the TEF approach could
be applied to the effects of PCBs on postnatal neurobehavioural development.
This would include research on an appropriate animal model to determine
whether the critical toxicological mechanism is mediated through the Ah
receptor. 5. The reproductive toxicity of complex PCB mixtures such as
those found in foods will depend on the identifies and relative proportions
of individual PCB congeners in the mixture. It is not possible to give
an accurate estimate of a NOAEL or LOAEL from the reproduction studies
using commercial PCB mixtures which could be readily applied to the safety
assessment of PCBs present as contaminants in food. 6. It is concluded
that the data presented in this paper support the hypothesis that there
is no satisfactory method derived from the available studies in laboratory
animals for evaluating the potential risk of adverse effects on reproduction
posed by contamination of foods with PCBs. (Battershill, 1994)
Study #23
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PCB commercial mixture Aroclor 1254 inhibits uptake of lymphocyte
DG and monocyte DG (2 types of leukocytes)
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inhibition of glucose uptake in human leukocytes by PCB Aroclor-1254
appears to be independent of adenosine-triphosphatase inhibition
The effect of Aroclor-1254 (11097691) on glucose uptake in
human leukocytes was examined. Leukocytes were separated from heparinized
blood samples obtained from healthy adults. Leukocytes (lymphocytes, monocytes,
and neutrophils) were resuspended in culture medium without heat inactivated
calf serum. Aroclor-1254 was dissolved in dimethyl-sulfoxide and diluted
with 1 milliliter leukocyte suspension to the appropriate concentrations.
Twenty minutes after the addition of Aroclor-1254, carbon-14 labeled 2-deoxyglucose
(DG) was added to the medium, and the mixture was incubated at 37 degrees-C
for 1 hour. After incubation the suspension of cells was centrifuged and
washed once. The radioactivity associated with the cell pellet was counted
in a beta counter. Neutrophil DG uptake was not inhibited by Aroclor-1254.
Aroclor-1254 inhibition of lymphocyte DG uptake was dependent on
time of exposure. A minimum of 60 minutes of incubation with Aroclor-1254
was needed before any significant inhibition was detected. Monocyte
DG uptake was also inhibited by Aroclor-1254. The authors conclude
that the observed inhibition of glucose uptake by Aroclor-1254 appears
to be independent of adenosine-triphosphatase inhibition. (Lee et al, 1980)
Study #24
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certain PCB types had no effects on mitogen-induced DNA synthesis
and immunoglobulin synthesis by lymphocytes
The structural similarities between polybrominated diphenyl
ethers and immunotoxic halogenated aromatic compounds suggest that the
polybrominated diphenyl ethers might affect the immune system. The present
study was undertaken to investigate the immunological effects of some purified
PBDE-congeners on human lymphocyte function in vitro. Polychlorinated
biphenyl congeners were also included in the study. Mitogen-induced
DNA synthesis and immunoglobulin synthesis by lymphocytes from blood donors
were examined following polybrominated diphenyl ether or polychlorinated
biphenyl exposure in vitro in order to determine the immunotoxic potential
of these substances. No effects on mitogen-induced proliferation or
immunoglobulin synthesis were observed after exposure of cells to concentrations
up to 10(-5) M. The negative findings in this study indicate that certain
functions of human peripheral lymphocytes, i.e. proliferation and immunoglobulin
synthesis, are insensitive to the direct action of polybrominate
(incomplete abstract) (Fernlof et al, 1997)
Study #25
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research methods have been developed to study PCB impacts
on human leukocytes
The use of in-vitro studies to elucidate the biochemical
mechanisms involved in the effects of polychlorinated biphenyls (PCBs)
on leukocyte activity was examined. A review of the effects of PCB exposure
on the immune system and other organ systems was presented. Methods used
for studying the effects of PCBs on leukocyte cell cultures were described.
These included the separation of cell populations from whole peripheral
blood by centrifugation and the assessment of chemical toxicity by examining
various cell activities and cell viability. Tests for the evaluation of
lymphocyte function were described such as the mitogenic response, rosette
formation with sheep red blood cells, the removal and regeneration of receptors
for rosettes, and lymphokine secretions. Tests for the evaluation of neutrophil
function have included chemotactic responses, lysosomal enzyme release,
phagocytic activity, oxygen consumption, and assessment of the phagocytic
and cytotoxic activities in response to Staphylococcus. (Lee, 1992)
Study #26
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interference with E-rosette formation and human T-lymphocyte
function
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direct action on lymphocytes, for example, interference with
epitopes of the CD 2-receptor or specific membrane function
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consistent with the delayed type of hypersensitivity reaction
seen in humans
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study used PCBs 28 and 153, and other chemicals
Efforts were undertaken to determine the ability of several
drugs and environmental contaminants to affect immune responses and immune
parameters. A modified E-rosette inhibition assay using human lymphocytes
was used to investigate the effects of propanolol (525666), flunarizine,
dihydroergotamine (511126), 2,4,4'-trichlorbiphenyl, 2,2'4,4'5,5'-hexachlorbiphenyl
(35065271), pentachlorphenol (87865), and DDE (72559). The two hydrophobic
drugs, flunarizine and propranolol, and dihydroergotamine did not interfere
with T-lymphocyte function at low concentrations comparable to those encountered
in therapy. The present results did indicate interference with E-rosette
formation and T-lymphocyte function by environmental contaminants in a
manner similar to the early pregnancy factor (EPF). The authors speculate
that the tested environmental contaminants elicit their immunosuppressive
effects by a similar mechanism. These findings may somewhat explain the
discrepancy between in-vivo and in-vitro data and may offer a perspective
for further investigation of the underlying mechanisms of immunomodulating
effects of environmental contaminants. The effects observed in the more
sensitive modified E-rosette assay suggest a direct action on lymphocytes,
for example, interference with epitopes of the CD 2-receptor or specific
membrane function. These findings are consistent with in-vivo impairment
of cellular immune responses in animals and of the delayed type of hypersensitivity
reaction in man. As a bioassay using human lymphocytes, the E-rosette
assay is an extremely sensitive test for the detection of interference
with T-cell function at nanomolar and possibly picomolar concentrations.
(Heinzow et al, 1989)
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