Immunotoxicity of stainless-steel nanoparticles obtained after 3D printing.

This study aims to investigate the in vitro effects of nanoparticles (NPs) produced during the selective laser melting (SLM) of 316 L stainless steel metal powder on the immune response in a human blood model. Experimental data did not reveal effect on viability of 316 L NPs for the tested doses. Functional immune assays showed a significant immunosuppressive effect of NPs. There was moderate stimulation (117%) of monocyte phagocytic activity without significant changes in phagocytic activity and respiratory burst of granulocytes. A significant dose-dependent increase in the levels of the pro-inflammatory cytokine TNF-a was found in blood cultures treated with NPs. On the contrary, IL-8 chemokine levels were significantly suppressed. The levels of the pro-inflammatory cytokine IL-6 were reduced by only a single concentration of NPs. These new findings can minimise potential health risks and indicate the need for more research in this area.

Association of Inflammatory and Oxidative Status Markers with Metabolic Syndrome and Its Components in 40-to-45-Year-Old Females: A Cross-Sectional Study.

Oxidative stress and sterile inflammation play roles in the induction and maintenance of metabolic syndrome (MetS). This study cohort included 170 females aged 40 to 45 years who were categorized according to the presentation of MetS components (e.g., central obesity, insulin resistance, atherogenic dyslipidemia, and elevated systolic blood pressure) as controls not presenting a single component (n = 43), those with pre-MetS displaying one to two components (n = 70), and females manifesting MetS, e.g., ≥3 components (n = 53). We analyzed the trends of seventeen oxidative and nine inflammatory status markers across three clinical categories. A multivariate regression of selected oxidative status and inflammatory markers on the components of MetS was performed. Markers of oxidative damage (malondialdehyde and advanced-glycation-end-products-associated fluorescence of plasma) were similar across the groups. Healthy controls displayed lower uricemia and higher bilirubinemia than females with MetS; and lower leukocyte counts, concentrations of C-reactive protein, interleukine-6, and higher levels of carotenoids/lipids and soluble receptors for advanced glycation end-products than those with pre-MetS and MetS. In multivariate regression models, levels of C-reactive protein, uric acid, and interleukine-6 were consistently associated with MetS components, although the impacts of single markers differed. Our data suggest that a proinflammatory imbalance precedes the manifestation of MetS, while an imbalance of oxidative status accompanies overt MetS. Further studies are needed to elucidate whether determining markers beyond traditional ones could help improve the prognosis of subjects at an early stage of MetS.

Titanium Dioxide Nanoparticles Modulate Systemic Immune Response and Increase Levels of Reduced Glutathione in Mice after Seven-Week Inhalation.

Titanium dioxide nanoparticles (TiO2 NPs) are used in a wide range of applications. Although inhalation of NPs is one of the most important toxicologically relevant routes, experimental studies on potential harmful effects of TiO2 NPs using a whole-body inhalation chamber model are rare. In this study, the profile of lymphocyte markers, functional immunoassays, and antioxidant defense markers were analyzed to evaluate the potential adverse effects of seven-week inhalation exposure to two different concentrations of TiO2 NPs (0.00167 and 0.1308 mg TiO2/m3) in mice. A dose-dependent effect of TiO2 NPs on innate immunity was evident in the form of stimulated phagocytic activity of monocytes in low-dose mice and suppressed secretory function of monocytes (IL-18) in high-dose animals. The effect of TiO2 NPs on adaptive immunity, manifested in the spleen by a decrease in the percentage of T-cells, a reduction in T-helper cells, and a dose-dependent decrease in lymphocyte cytokine production, may indicate immunosuppression in exposed mice. The dose-dependent increase in GSH concentration and GSH/GSSG ratio in whole blood demonstrated stimulated antioxidant defense against oxidative stress induced by TiO2 NP exposure.

Copper Oxide Nanoparticles Stimulate the Immune Response and Decrease Antioxidant Defense in Mice After Six-Week Inhalation.

Copper oxide nanoparticles (CuO NPs) are increasingly used in various industry sectors. Moreover, medical application of CuO NPs as antimicrobials also contributes to human exposure. Their toxicity, including toxicity to the immune system and blood, raises concerns, while information on their immunotoxicity is still very limited. The aim of our work was to evaluate the effects of CuO NPs (number concentration 1.40×106 particles/cm3, geometric mean diameter 20.4 nm) on immune/inflammatory response and antioxidant defense in mice exposed to 32.5 µg CuO/m3 continuously for 6 weeks. After six weeks of CuO NP inhalation, the content of copper in lungs and liver was significantly increased, while in kidneys, spleen, brain, and blood it was similar in exposed and control mice. Inhalation of CuO NPs caused a significant increase in proliferative response of T-lymphocytes after mitogenic stimulation and basal proliferative activity of splenocytes. CuO NPs significantly induced the production of IL-12p70, Th1-cytokine IFN-γ and Th2-cytokines IL-4, IL-5. Levels of TNF-α and IL-6 remained unchanged. Immune assays showed significantly suppressed phagocytic activity of granulocytes and slightly decreased respiratory burst. No significant differences in phagocytosis of monocytes were recorded. The percentage of CD3+, CD3+CD4+, CD3+CD8+, and CD3-CD19+ cell subsets in spleen, thymus, and lymph nodes did not differ between exposed and control animals. No changes in hematological parameters were found between the CuO NP exposed and control groups. The overall antioxidant protection status of the organism was expressed by evaluation of GSH and GSSG concentrations in blood samples. The experimental group exposed to CuO NPs showed a significant decrease in GSH concentration in comparison to the control group. In summary, our results indicate that sub-chronic inhalation of CuO NPs can cause undesired modulation of the immune response. Stimulation of adaptive immunity was indicated by activation of proliferation and secretion functions of lymphocytes. CuO NPs elicited pro-activation state of Th1 and Th2 lymphocytes in exposed mice. Innate immunity was affected by impaired phagocytic activity of granulocytes. Reduced glutathione was significantly decreased in mice exposed to CuO NPs.

The Cell Surface Markers Expression in Postmenopausal Women and Relation to Obesity and Bone Status.

The age-related changes and hormonal deprivation in postmenopausal women are associated with the immune response alteration. The excessive fat accumulation, local and systemic inflammation may lead to dysregulation in immune function and relevant health problems, including obesity and osteoporosis. We analyzed the expression of cell surface markers in the venous blood specimens, stained with fluorophores-conjugated monoclonal antibodies and analysed by multicolour flow cytometry. The significant changes of cytotoxic, naive, and memory T-lymphocytes, plasmacytoid dendritic cells (DCs) were in postmenopausal women versus fertile women. Body mass index (BMI) affected markedly the cell surface expression of CD265/RANK. Osteoporosis is linked to reduced percentage of plasmacytoid DCs, and elevated natural Treg cells (p < 0.05). The confounding factors such as women age, BMI, bone mineral density (BMD), waist size and tissue fat affect the expression of RANK on myeloid DCs and CD40L on T-lymphocytes that might be the immunophenotypic modulators after menopause.

The effect of core and lanthanide ion dopants in sodium fluoride-based nanocrystals on phagocytic activity of human blood leukocytes.

Sodium fluoride-based ß-NaLnF4 nanoparticles (NPs) doped with lanthanide ions are promising materials for application as luminescent markers in bio-imaging. In this work, the effect of NPs doped with yttrium (Y), gadolinium (Gd), europium (Eu), thulium (Tm), ytterbium (Yb) and terbium (Tb) ions on phagocytic activity of monocytes and granulocytes and the respiratory burst was examined. The surface functionalization of <10-nm NPs was performed according to our variation of patent pending ligand exchange method that resulted in meso-2,3-dimercaptosuccinic acid (DMSA) molecules on their surface. Y-core-based NCs were doped with Eu ions, which enabled them to be excited with UV light wavelengths. Cultures of human peripheral blood (n = 8) were in vitro treated with five different concentrations of eight NPs for 24 h. In summary, neither type of nanoparticles is found toxic with respect to conducted test; however, some cause toxic effects (they have statistically significant deviations compared to reference) in some selected doses tested. Both core types of NPs (Y-core and Gd-core) impaired the phagocytic activity of monocytes the strongest, having minimal or none whatsoever influence on granulocytes and respiratory burst of phagocytic cells. The lowest toxicity was observed in Gd-core, Yb, Tm dopants and near-infrared nanoparticles. Clear dose-dependent effect of NPs on phagocytic activity of leukocytes and respiratory burst of cells was observed for limited number of samples.

Hydrophobic sodium fluoride-based nanocrystals doped with lanthanide ions: assessment of in vitro toxicity to human blood lymphocytes and phagocytes.

In vitro immunotoxicity of hydrophobic sodium fluoride-based nanocrystals (NCs) doped with lanthanide ions was examined in this study. Although there is already a significant amount of optical and structural data on NaYF4 NCs, data on safety assessment are missing. Therefore, peripheral whole blood from human volunteers was used to evaluate the effect of 25 and 30 nm hydrophobic NaYF4 NCs dissolved in cyclohexane (CH) on lymphocytes, and of 10 nm NaYF4 NCs on phagocytes. In the concentration range 0.12-75 µg cm(-2) (0.17-106 µg ml(-1) ), both 25 and 30nm NaYF4 NCs did not induce cytotoxicity when measured as incorporation of [(3) H]-thymidine into DNA. Assessment of lymphocyte function showed significant suppression of the proliferative activity of T-lymphocytes and T-dependent B-cell response in peripheral blood cultures (n = 7) stimulated in vitro with mitogens phytohemagglutinin (PHA) and pokeweed (PWM) (PHA > PWM). No clear dose-response effect was observed. Phagocytic activity and respiratory burst of leukocytes (n = 5-8) were generally less affected. A dose-dependent suppression of phagocytic activity of granulocytes in cultures treated with 25 nm NCs was observed (vs. medium control). A decrease in phagocytic activity of monocytes was found in cells exposed to higher doses of 10 and 30 nm NCs. The respiratory burst of phagocytes was significantly decreased by exposure to the middle dose of 30 nm NCs only. In conclusion, our results demonstrate immunotoxic effects of hydrophobic NaYF4 NCs doped with lanthanide ions to lymphocytes and to lesser extent to phagocytes. Further research needs to be done, particularly faze transfer of hydrophobic NCs to hydrophilic ones, to eliminate the solvent effect.

Association between the human immune response and body mass index.

The aim of this study was to determine the strength of the association between the human immune response and body mass index (BMI) and whether differences exist in the effects of obesity on selected immune parameters between men and women. Two hundred ninety participants were divided into groups according to sex and BMI. Parameters CD3, CD4, CD8, CD16+56, CD19, HLADR, CD11b, CD11c, and CD54 were quantified. Leukocyte and differential counts were performed. We observed elevation with regard to the normal weight group in the parameters of white blood cells, neutrophils, monocytes, CD3, CD4, CD19, and CD11b for the whole study group. A decrease was observed in the expression of CD16+56. The effect of BMI on the immune system was much more apparent in women. BMI was correlated with the majority of the measured parameters, reflecting a strong association between BMI and the human immune system.

Changes in immunologic parameters of humoral immunity and adipocytokines in obese persons are gender dependent.

The aim of this study was to investigate several immunologic parameters using of immunonephelometry and adipocytokines by the enzyme immunoassay and their changes in different states of obesity. Obesity is considered to involve a state of chronic low-grade inflammation, with links between adipose cells and the immune system. We found significantly higher complement C3 levels in all obese subjects. Levels of the complement C4 were significantly higher in obese women, but not in men, when compared with the corresponding group of normal weight subjects. The increase in C-reactive protein concentrations was significant in both obese and morbidly obese women, but only in morbidly obese men. No significant differences in tumor necrosis factor-α, interleukin-6, interleukin-10, and soluble intercellular adhesion molecule-1 were found. sE-selectin levels were higher in both overweight and obese women but only in morbidly obese men. We found decreased adiponectin concentrations in obese and morbidly obese women. Concentrations of leptin were significantly higher only in obese men (p < 0.05), whereas in women the increase in leptin levels was significant in overweight, obese, and morbidly obese subjects. In conclusion, our results demonstrate elevated levels of C3, C-reactive protein, sE-selectin, and leptin in obese women and men. In obese women, we also observed increased concentrations of C4 and decreased levels of adiponectin.