The gut cytokine balance as a target of lead toxicity (original) (raw)
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Lead Differentially Modifies Cytokine Productionin Vitroandin Vivo
Toxicology and Applied Pharmacology, 1996
, e.g., after only a 1-week exposure to Pb, Lead Differentially Modifies Cytokine Production in Vitro and host resistance of CBA/J mice to Listeria monocytogenes in Vivo. HEO, Y., PARSONS, P. J., AND LAWRENCE, D. A. (1996). was compromised (Lawrence, 1981c). Pb-induced inhibition Toxicol. Appl. Pharmacol. 138, 149-157.
Immunologic Research, 2003
Lead, a potential human carcinogen, is a ubiquitous environmental pollutant in the industrial environment that poses a serious threat to human health. This toxic lead can modulate the immune response of animals as well as humans. In some instances, the immune system appears to be exquisitely sensitive to lead as compared with other toxicological parameters. Both stimulation and suppression of immune response have been demonstrated in lead exposed animals and humans depending on the T helper (Th)1 vs Th2 response. Although the majority of data accumulated to date pertains to the effects of lead in small laboratory rodents, there is little reason to believe that similar quantifiable effects do not occur in domestic and food-producing animals owing to basic functional similarities of the immune system of mammals. In this review, we have discussed the immunomodulatory role of the toxic heavy metal, lead, on cellular and humoral components of the immune system with particular reference to effector cells such as B cells, T cells, natural killer (NK) cells, and soluble mediators such as cytokines, chemokines, and nitric oxide (NO).
Journal of immunotoxicology, 2016
Many investigators have posited on the significant influence of lead on the immune system function. However, available data on this topic are not conclusive. Therefore, a study was undertaken to examine associations between lead exposure and levels of cytokines related to the T-helper (TH)-1, TH2, and TH17 types of immune response in humans. For these analyses, three population groups were examined: the first consisted of male workers exposed to lead for a short period of time (36-44 days); the second included male workers chronically exposed to lead (13 ± 10 years); and a control group that was composed of male administrative workers with blood lead levels (BLL) < 10 μg/dl. BLL were determined for all study subjects. Thereafter, serum samples were analyzed for the levels of interleukin (IL)-2 (IL-2), IL-4, IL-5, IL-12, IL-13, IL-17A, and interferon (IFN)-γ using a multi-analyte system. The results indicated that the levels of IFNγ IL-2, IL-12 (related to TH1 cells), IL-4, IL-5, ...
Interleukin-12 Promotes Enhanced Resistance toInfection of Lead-Exposed Mice
Toxicology and Applied Pharmacology, 1997
The heavy metal lead (Pb) has been shown to downregulate various parameters of cell-mediated immune (CMI) responses. This inhibition of CMI responses by Pb is exemplified by a higher mortality rate upon infections with sublethal doses of a variety of pathogens. Unlike Pb, which lowers host resistance, interleukin-12 (IL-12) exerts a substantial stimulatory influence on the host response to intracellular bacteria such as Listeria monocytogenes. To explore the influence of IL-12 in mice rendered susceptible to Listerial infection by oral exposure to Pb, we determined bacterial burdens and production of interferon gamma (IFN-␥). As expected, Pb-exposed mice had increased morbidity due to higher Listerial titers as compared to control mice. However, administration of exogenous IL-12 reversed the Pbinduced inhibition of host defense and boosted the resistance of the non-Pb-treated mice. The enhanced CMI responses observed in both IL-12-treated groups were accompanied with elevations of IFN-␥ in the sera and spleens. Significant reduction in the number of viable Listeria in Pb-exposed mice upon IL-12 administration suggests that the processes downstream of IL-12 production were intact in the Pb-exposed mice and that the inhibition by Pb was due to the lack of functional IL-12. Alternatively, the exogenous IL-12 may have overcome a downstream effect by enhancing an secondary pathway. Support for the former hypothesis is based on the observation that Pb induced elevated levels of p40 splenic messenger RNA since increased p40 expression would result from lack of IL-12 formation. Contrary to the IFN-␥ levels, significantly higher levels of IL-6 and corticosterone were observed in the sera and spleens of Pb-exposed mice upon infection, suggesting heightened stress in the absence of IL-12. Overall, the results suggest that an environmental pollutant such as Pb can enhance the stress response, which naturally occurs during an infection, and can further compromise health by lowering host resistance by altering cytokine levels.
Lead induced modulation of splenic macrophage responses on humoral and cell mediated immunity
Acta Microbiologica et Immunologica Hungarica, 2004
The heavy metal lead is an environmental toxic material that can induce pathophysiological changes in many organ systems. Previous studies have shown the effects of lead exposure on immune cells in different experimental animals, however, the mechanism of their influence on the immune system is unclear. We reported that in vivo lead exposure inhibits phagocytosis, nitric oxide release, induces DNA fragmentation suggesting the apoptotic death of the target cell. We have also presented evidence that inhibition of macrophage functional responses implicated alteration of humoral and cell mediated immunity. In vivo exposure to lead acetate alters the phagocytic capacity of splenic macrophages as evident from the reduction of phagocytic index of control from 19,792±1385.69 to 8893 ± 893 in the treated group. The amount of nitric oxide released by the control cell 2.25 ± 0.125 µM is also reduced to 1.9375 ± 0.0625 µM upon in vivo lead treatment. Functional integrity of the target cell is also decreased after lead exposure as obtained from the percentage of DNA fragmentation. Control group shows 33.29 ± 0.11% of fragmented DNA, which is enhanced to 42.43 ± 0.725% following the lead treatment. A greater percentage of DNA fragmentation upon lead treatment probably indicating that the heavy metal induces apoptosis. The humoral immune response is also altered after lead exposure as indicated by the decrease of the antibody titre in control group from 1:2048 to1:128 in the treated group. From the DTH reaction, it was observed that the mean diameter of swollen foot pad of control mice is 0.329 ± 0.15 cm and that of lead treated mice is 0.274 ± 0.056 cm. It can, therefore, be suggested that lead inhibits normal functional activities of splenic leukocytes, particularly phagocytosis and also affects the functional integrity of cells by inducing DNA fragmentation. The study may demonstrate the usefulness of investigation of humoral immune system and leukocyte functions as sensitive parameters in detecting the effects of lead toxicity.
Nine kinds of novel cytokines identified in children with lead exposure
E3S Web of Conferences
Lead (Pb) is a neurotoxic heavy metal element with many recognized adverse health side effects, and its main target of lead toxicity is the central nervous system. The mechanism of lead toxicity is still uncertain. However, there are few studies investigated the cytokines changes caused by lead exposure in children. The BLLs was quantified using flame atomic absorption spectroscopy. The novel cytokines were detected by RayBio@ Human Cytokine Antibody Array. A total of 4 children with elevated blood lead levels (BLLs) and 4 children with low BLLs were chosen in the study. Volcano plot analysis was performed to identify significant proteins, with the criteria: P value <0.05 and log2 fold change >1. The mean BLLs of children with elevated BLLs (5.675±1.018 μg/dL) has significant difference compared with those with low BLLs (1.975±0.3966 μg/dL) (P=0.0148, t=3.385). And 9 kinds of novel cytokines were identified. The expression of IL-6, IL-8 and IL-17 was significantly up-regulated...
Archives of Environmental Contamination and Toxicology, 2000
Evidence implicating oxidative stress in toxicity during lead intoxication in vivo has opened new avenues for investigation of the mechanisms of lead-induced immunosuppression. The current study explores the possibility that lead-induced oxidative stress contributes to the immunosuppression observed during lead poisoning. Fisher 344 rats were exposed to 2,000 ppm lead acetate in their drinking water for 5 weeks. One week following removal of lead from the drinking water, significant reductions in serum levels of IgA, IgM, and IgG were detected. Significant increases in oxidative damage, based on malondialdehyde (MDA) content, were observed in peripheral blood mononuclear cells (PMCs) collected during the same experiments. In addition, MDA content increased in livers from lead-exposed rats. Following 5 weeks of lead exposure, administration of either 5.5 mmol/kg N-acetylcysteine (NAC) or 1 mmol/kg meso-2,3-dimercaptosuccinic acid (DMSA) in the drinking water for 1 week significantly reversed the inhibitory effects of lead on serum immunoglobulin (Ig) levels. Also, all parameters indicative of oxidative stress returned to control levels. These results suggest that oxidative stress contributes to suppressed serum Ig levels during lead intoxication in vivo, and that intervention with either a thiol antioxidant (NAC) or a metal chelator (DMSA) will alleviate this lead-induced suppression by correcting the prooxidant/antioxidant imbalance caused by lead exposure.
The Immunotoxicity of Chronic Exposure to High Levels of Lead: An Ex Vivo Investigation
Toxics
Lead (Pb) is a toxic metal known for its wide-ranging adverse health effects. However, a compound of Pb is still used in the caulking process to repair wooden fishing boats. The present study aimed to measure Pb exposure and its immunologic effects in boatyard workers in Nakhon Si Thammarat province, Thailand, in comparison with an age-matched control group of farmers. The age, body mass index, and smoking history in workers (n = 14) and controls (n = 16) did not differ. The median blood Pb concentration was 8.7-fold higher in workers than controls (37.1 versus 4.3 µg/dL, p < 0.001). Workers had 8.4% lower phagocytic active cells than controls (89.9% versus 98.1%, p = 0.019). In response to a mitogen stimulation, the peripheral blood mononuclear cells (PBMCs) from workers produced 2-fold higher ratios of interleukin-4 (IL-4) to interferon-γ than the PBMCs from controls (p = 0.026). Furthermore, Pb-exposed workers had 33.9% lower cytotoxic T (Tc) cells than controls (24.3% versus ...
The effect of lead acetate on the immune response in mice
Toxicology and Applied Pharmacology, 1981
Immunological studies demonstrated that lead suppressed macrophage-dependent immune responses. The functional activity of the macrophage was evaluated by the Mishell-Dutton, in vitro, antibody production technique. Lead suppressed the immune response when the macrophage-dependent antigens, sheep red blood cells or dinitrophenyl-Ficoll, were utilized, but the response to the macrophage-independent antigen, Escherichia coli lipopolysaccharide, was not suppressed. The macrophage substitute, 2-mercaptoethanol, caused restoration of the lead-suppressed immune response. The immune responses seen in the four combinations of adherent/nonadherent and lead-exposed/non-lead-exposed cell cultures, were suppressed only in cultures containing lead-exposed adherent cells. The immunosuppressive effects of lead were produced at relatively low lead exposures as indicated by the blood lead concentrations. Weight gains and water consumption were not affected by these lead exposures. The low level lead exposure effects manifested by immunosuppression indicate that immune dysfunction is a sensitive indicator of lead exposure.