Recent reports raised concerns over immune effects of chlorinated pollutants[ 9 — 12 ]. Experimental animal studies and in vitro assays with a few selected PCBs show immunosuppressive effects of PCBs[ 12 — 19 ]. Similarly, accidental exposures to high levels of PCBs resulted in immunosuppressive effects in humans[ 20 ]. Among the different testing schemes recommended to assess immunotoxicity in humans, the most common tests involve routine hematologic parameters, such as blood counts with differentials, serum clinical chemistry measures, and more specific tests evaluating cellular and humoral immune response[ 21 ].
Total white blood cell WBC count has been considered as a useful marker of immune changes in humans, with absolute numbers providing more reliable information than percentages[ 21 ]. The main objective of this study is to examine possible associations between blood levels of selected PCBs, organochlorine pesticides and common hematologic and immune markers, such as blood count and blood biochemistry data in a group representative of the United States general population using data of the National Health Examination and Survey It aims to evaluate the health and nutritional status of adults and children in the United States and the survey combines interviews, physical examinations and laboratory data.
More detailed descriptions of analytical methods have been reported previously[ 22 — 24 ]. Since analytical detection limits of serum PCBs varied greatly in previous cycles, all analyses were limited to the most recent survey cycle. The group of DL PCBs was a combination of dioxin like chemicals such as polychlorinated dibenzofurans, polychlorinated dibenzo-p-dioxins, coplanar polychlorinated biphenyls, and mono-ortho-substituted polychlorinated biphenyls.
The following congeners were included in the total of 17 NDL PCBs: 28; 52; 66; 74; 99; ; ; ; ; ; ; ; ; ; ; ; Complete blood count CBC measurements with 5-part differential in whole blood were obtained based on the Beckman Coulter method of counting and sizing, in combination with an automatic diluting and mixing device for sample processing, and a single beam photometer for hemoglobinometry as described previously[ 25 ]. Routine biochemistry profile analysis was performed using Beckman Synchron LX20 analyzer[ 25 ]. Biochemistry profiles included all routine measurements, except for measures of triglycerides and cholesterol.
These blood lipid values were excluded from analyses, since all chlorinated chemical biomarker levels were adjusted for total lipids that were calculated based on blood triglyceride and cholesterol levels. The biochemistry variables included: albumin, alanine aminotransferase ALT , aspartate aminotransferase AST , alkaline phosphatase, blood urea nitrogen, total calcium, bicarbonate, gamma glutamyl transferase GGT , glucose, iron, lactate dehydrogenase LDH , phosphorus, bilirubin, total protein, uric acid, creatinine, sodium, potassium, chloride, osmolality, and globulin.
A detailed list of these variables is provided elsewhere[ 26 , 27 ]. Additionally, level of serum C-Reactive Protein was evaluated as a dependent variable. All statistical analyses were conducted using SAS system version 9. Age and gender are common factors influencing hematologic and immunity markers in the general population[ 21 , 28 ] and thus have been considered as potential confounders in all comparisons. In six cases see below for list there were no individuals with a below LOD measurement. If there were fewer than individuals below LOD for a compound, the sample was simply split into quartiles of approximately individuals per quartile.
If there were or more individuals below LOD, they alone formed the first exposure group, i. In summary, each individual had 41 indicator variables, one for each PCB, OCP, which ranged in value from 0 to 3, with 0 indicating the lowest level of exposure to a particular compound. For the Total DL variable, the sum of the 19 indicator variables that ranged in value from 0 to 3 could result in a score ranging from 0 to Total NDL ranged from 0 to Once these sums were computed, individuals were divided into 4 exposure groups for each.
The cutoff scores for the four groups for Total DL were: , , , and For Total NDL, the cutoff scores were: , , , and In summary, each individual had two additional indicator variables, for DL and NDL that ranged from 0 to 3, with 0 indicating the lowest level of exposure to a particular combination of compounds. For each test of a dependent blood variable e. Since all statistical tests were specified a priori, we followed recommendations to report p-values rather than adjust for multiple comparisons[ 29 , 30 ].
Serum levels of PCBs DL and NDL and of organochlorine pesticides are positively associated with age and were highest among the oldest members of the population. Polychlorinated dibenzofurans such as F08 and F10 or coplanar polychlorinated biphenyls such as TC2 showed fewer and weaker correlations with NDL PCBs in comparison to the other dioxin like compounds see Additional file 1. While we observed changes in the distribution percentages of blood cells, the absolute numbers of red and white blood cells decreased consistently as PCB levels increased. Difference between the highest and lowest exposure groups reached 1,, of WBC per ml of blood for PCB Additional file 2 , lines For most DL PCBs, even though a similar decline of WBC was observed at the highest exposure levels, the difference in total cell counts did not reach statistical significance Additional file 2.
The difference in mean RBC number between the highest and lowest exposure groups of PCB was million cells per ml of blood.
Serum Mirex: Lymphocyte number and segmented neutrophil numbers appeared to be lower in the highest exposure groups, while the percentages of basophils and monocytes appeared to be higher. Mean cell total hemoglobin and hemoglobin concentrations were lower in the highest exposure group, while WBC count was significantly lower in this group. For trans-nonachlor and oxychlordane: Lymphocyte number and segmented neutrophils numbers increased as the pesticide levels increased. A few of the analytes were significantly different across categories of pesticide biomarkers.
Those differences were as follows:. Serum glucose appeared to be higher in the second exposure group, but was at lower concentrations for the third and fourth highest exposure groups. Regression analyses were repeated in three subsets of the data to evaluate the influence of cancer, possible autoimmune disease Type 1D and RA , and anemia.
Statistically significant results of these analyses are presented in supplementary files Additional files 3 , 4 , 5 , 6 , 7 and 8. Overall, changes in blood parameters showed a consistent pattern for all exposure types in these different subset analyses. Despite a manufacturing ban over three decades ago, measurable amounts of PCBs and chlorinated pesticides are present in serum samples obtained recently from the general population. Highest serum levels were observed in the elderly which is consistent with previous reports[ 31 — 33 ].
The age difference may reflect bioaccumulation of these chemicals over the years, the reduced exposures faced by the younger generation, or both. We report possible associations between selected chlorinated compounds and common blood measures involving immune cells and blood biochemistry.
Daniel et al[ 34 ] examined cellular and humoral immune response among individuals with occupational exposures to PCBs. Overall, patients with higher levels of these persistent chemicals in their blood had lower levels of T lymphocyte counts, lower INF-gamma levels, and higher GGT plasma levels[ 34 ]. Somewhat consistent findings have been reported for cases of prenatal exposure to PCBs, in which increased risk of early childhood infections was observed in different cohorts across the world[ 9 , 35 — 37 ]. Among the Inuit population, who are known to have higher levels of exposures to organochlorines[ 38 ], umbilical cord blood levels of PCBs were associated with increased incidence of acute otitis media and lower respiratory tract infections during the first five years of life[ 36 ].
Similarly, prenatal exposure to PCBs has been linked to increased risks of developing infections within the first three years of life in a Norwegian mother and child cohort[ 35 ]. Accidental PCB poisoning through consumption of contaminated rice bran oil in Taiwan in showed marked immunosuppressive effects among those affected, with many patients suffering from a wide range of infections[ 20 ]. Alexander, D. Aryl-hydrocarbon receptor is an inhibitory regulator of lipid synthesis and of commitment to adipogenesis. Kerley-Hamilton, J.
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