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Exposure to Palladium Nanoparticles Affects Serum Levels of Cytokines in Female Wistar Rats.

Iavicoli I, Fontana L, Corbi M, Leso V, Marinaccio A, Leopold K, Schindl R, Sgambato A - PLoS ONE (2015)

Bottom Line: In this context, the evaluation of the possible effects exerted by palladium nanoparticles (Pd-NPs) on the immune system is essential to comprehensively assess palladium immunotoxic potential.The highest concentration of Pd-NPs (12 μg/kg) induced a significant increase of IL-1α, IL-4, IL-6, IL-10, IL-12, GM-CSF and INF-γ compared to controls.Our findings did not show an imbalance between cytokines produced by CD4+ T helper (Th) cells 1 and 2, thus suggesting a generalized stimulation of the immune system with a simultaneous activation and polarization of the naïve T cells towards Th1 and Th2 phenotype.

View Article: PubMed Central - PubMed

Affiliation: Institute of Public Health, Section of Occupational Medicine, Catholic University of the Sacred Heart, Largo Francesco Vito 1, 00168, Rome, Italy.

ABSTRACT

Background: Information currently available on the impact of palladium on the immune system mainly derives from studies assessing the biological effects of palladium salts. However, in the last years, there has been a notable increase in occupational and environmental levels of fine and ultrafine palladium particles released from automobile catalytic converters, which may play a role in palladium sensitization. In this context, the evaluation of the possible effects exerted by palladium nanoparticles (Pd-NPs) on the immune system is essential to comprehensively assess palladium immunotoxic potential.

Aim: Therefore, the aim of this study was to investigate the effects of Pd-NPs on the immune system of female Wistar rats exposed to this xenobiotic for 14 days, by assessing possible quantitative changes in a number of cytokines: IL-1α, IL-2, IL-4, IL-6, IL-10, IL-12, GM-CSF, INF-γ and TNF-α.

Methods: Twenty rats were randomly divided into four exposure groups and one of control. Animals were given a single tail vein injection of vehicle (control group) and different concentrations of Pd-NPs (0.012, 0.12, 1.2 and 12 μg/kg). A multiplex biometric enzyme linked immunosorbent assay was used to evaluate cytokine serum levels.

Results: The mean serum concentrations of all cytokines decreased after the administration of 0.012 μg/kg of Pd-NPs, whereas exceeded the control levels at higher exposure doses. The highest concentration of Pd-NPs (12 μg/kg) induced a significant increase of IL-1α, IL-4, IL-6, IL-10, IL-12, GM-CSF and INF-γ compared to controls.

Discussion and conclusions: These results demonstrated that Pd-NP exposure can affect the immune response of rats inducing a stimulatory action that becomes significant at the highest administered dose. Our findings did not show an imbalance between cytokines produced by CD4+ T helper (Th) cells 1 and 2, thus suggesting a generalized stimulation of the immune system with a simultaneous activation and polarization of the naïve T cells towards Th1 and Th2 phenotype.

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Mean serum levels of different cytokines expressed as percentage variation from control values (100%).The particular trend of the dose–response relationship observed for all cytokines (with a slight decrease at the lowest exposure dose and an increase thereafter with increasing exposure doses) would seem to suggest the presence of a hormetic phenomenon since in some cases the hormetic effects are typically graphed as a J-shaped dose response curve.
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pone.0143801.g004: Mean serum levels of different cytokines expressed as percentage variation from control values (100%).The particular trend of the dose–response relationship observed for all cytokines (with a slight decrease at the lowest exposure dose and an increase thereafter with increasing exposure doses) would seem to suggest the presence of a hormetic phenomenon since in some cases the hormetic effects are typically graphed as a J-shaped dose response curve.

Mentions: When analyzing the dose-response relationship obtained in our study, a rather particular trend was observed in all cytokine serum levels in the treated rats (Fig 2) with a slight decrease at the lowest exposure dose and an increase thereafter with increasing exposure doses. Comparably, Wilkinson et al. [31] observed a similar dose-response trend, with a decrease in the IL-8 release from PBEC and A549 cells at the lower concentration range and a slight tendency towards increased levels at the highest concentration. These dose–response relationships would seem to suggest the presence of a hormetic phenomenon since in some cases the hormetic effects are typically graphed as a J-shaped dose-response curve [53]. In fact, the term “hormesis” is used to describe dose-response curves where the response is reversed between low and high doses of a stressor (Fig 4) representing an index of biological plasticity at multiple levels of biological organization [54]. In this regard, it is possible to hypothesize that the decrease in cytokine levels determined at the lowest dose of exposure may be an adaptive compensatory process following an initial disruption in homeostasis induced by the NP chemical stress, which ultimately may induce increasing alterations in the cytokine concentrations at the higher treatment doses. Greater attention is being given to hormesis in the fields of aging and biogerontology, toxicology, pharmacology, public health and occupational medicine research, and recently this dose-response model has been shown to occur quite frequently also after exposure to different types of NPs [55]. To the best of our knowledge, this is the first time that a similar biphasic dose-response has been reported as a consequence of Pd-NP exposure. Obviously, this result should be considered with caution and further studies are needed. However, the possible presence, at low exposure levels, of effects that may be adaptive, non-adverse or even beneficial is an intriguing issue that deserves further attention particularly on account of the complex regulatory mechanisms of the immune system that favor a balance between pathogenic and protective Th cells and the crucial role that different Th subsets play in immunopathology [56].


Exposure to Palladium Nanoparticles Affects Serum Levels of Cytokines in Female Wistar Rats.

Iavicoli I, Fontana L, Corbi M, Leso V, Marinaccio A, Leopold K, Schindl R, Sgambato A - PLoS ONE (2015)

Mean serum levels of different cytokines expressed as percentage variation from control values (100%).The particular trend of the dose–response relationship observed for all cytokines (with a slight decrease at the lowest exposure dose and an increase thereafter with increasing exposure doses) would seem to suggest the presence of a hormetic phenomenon since in some cases the hormetic effects are typically graphed as a J-shaped dose response curve.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664404&req=5

pone.0143801.g004: Mean serum levels of different cytokines expressed as percentage variation from control values (100%).The particular trend of the dose–response relationship observed for all cytokines (with a slight decrease at the lowest exposure dose and an increase thereafter with increasing exposure doses) would seem to suggest the presence of a hormetic phenomenon since in some cases the hormetic effects are typically graphed as a J-shaped dose response curve.
Mentions: When analyzing the dose-response relationship obtained in our study, a rather particular trend was observed in all cytokine serum levels in the treated rats (Fig 2) with a slight decrease at the lowest exposure dose and an increase thereafter with increasing exposure doses. Comparably, Wilkinson et al. [31] observed a similar dose-response trend, with a decrease in the IL-8 release from PBEC and A549 cells at the lower concentration range and a slight tendency towards increased levels at the highest concentration. These dose–response relationships would seem to suggest the presence of a hormetic phenomenon since in some cases the hormetic effects are typically graphed as a J-shaped dose-response curve [53]. In fact, the term “hormesis” is used to describe dose-response curves where the response is reversed between low and high doses of a stressor (Fig 4) representing an index of biological plasticity at multiple levels of biological organization [54]. In this regard, it is possible to hypothesize that the decrease in cytokine levels determined at the lowest dose of exposure may be an adaptive compensatory process following an initial disruption in homeostasis induced by the NP chemical stress, which ultimately may induce increasing alterations in the cytokine concentrations at the higher treatment doses. Greater attention is being given to hormesis in the fields of aging and biogerontology, toxicology, pharmacology, public health and occupational medicine research, and recently this dose-response model has been shown to occur quite frequently also after exposure to different types of NPs [55]. To the best of our knowledge, this is the first time that a similar biphasic dose-response has been reported as a consequence of Pd-NP exposure. Obviously, this result should be considered with caution and further studies are needed. However, the possible presence, at low exposure levels, of effects that may be adaptive, non-adverse or even beneficial is an intriguing issue that deserves further attention particularly on account of the complex regulatory mechanisms of the immune system that favor a balance between pathogenic and protective Th cells and the crucial role that different Th subsets play in immunopathology [56].

Bottom Line: In this context, the evaluation of the possible effects exerted by palladium nanoparticles (Pd-NPs) on the immune system is essential to comprehensively assess palladium immunotoxic potential.The highest concentration of Pd-NPs (12 μg/kg) induced a significant increase of IL-1α, IL-4, IL-6, IL-10, IL-12, GM-CSF and INF-γ compared to controls.Our findings did not show an imbalance between cytokines produced by CD4+ T helper (Th) cells 1 and 2, thus suggesting a generalized stimulation of the immune system with a simultaneous activation and polarization of the naïve T cells towards Th1 and Th2 phenotype.

View Article: PubMed Central - PubMed

Affiliation: Institute of Public Health, Section of Occupational Medicine, Catholic University of the Sacred Heart, Largo Francesco Vito 1, 00168, Rome, Italy.

ABSTRACT

Background: Information currently available on the impact of palladium on the immune system mainly derives from studies assessing the biological effects of palladium salts. However, in the last years, there has been a notable increase in occupational and environmental levels of fine and ultrafine palladium particles released from automobile catalytic converters, which may play a role in palladium sensitization. In this context, the evaluation of the possible effects exerted by palladium nanoparticles (Pd-NPs) on the immune system is essential to comprehensively assess palladium immunotoxic potential.

Aim: Therefore, the aim of this study was to investigate the effects of Pd-NPs on the immune system of female Wistar rats exposed to this xenobiotic for 14 days, by assessing possible quantitative changes in a number of cytokines: IL-1α, IL-2, IL-4, IL-6, IL-10, IL-12, GM-CSF, INF-γ and TNF-α.

Methods: Twenty rats were randomly divided into four exposure groups and one of control. Animals were given a single tail vein injection of vehicle (control group) and different concentrations of Pd-NPs (0.012, 0.12, 1.2 and 12 μg/kg). A multiplex biometric enzyme linked immunosorbent assay was used to evaluate cytokine serum levels.

Results: The mean serum concentrations of all cytokines decreased after the administration of 0.012 μg/kg of Pd-NPs, whereas exceeded the control levels at higher exposure doses. The highest concentration of Pd-NPs (12 μg/kg) induced a significant increase of IL-1α, IL-4, IL-6, IL-10, IL-12, GM-CSF and INF-γ compared to controls.

Discussion and conclusions: These results demonstrated that Pd-NP exposure can affect the immune response of rats inducing a stimulatory action that becomes significant at the highest administered dose. Our findings did not show an imbalance between cytokines produced by CD4+ T helper (Th) cells 1 and 2, thus suggesting a generalized stimulation of the immune system with a simultaneous activation and polarization of the naïve T cells towards Th1 and Th2 phenotype.

Show MeSH
Related in: MedlinePlus