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.

How can an immunologist influence the occurrence of secondary infections in breast cancer? Real­life study.

BACKGROUND: Clinical manifestation of secondary immunodeficiency is responsible for the decrease in lfe quality in cancer­treated patients, which may result in administration delays, dose reductions, even in discontinuation of treatment. The main aim of presented study was to stress the possibility of influencing secondary infections with adjunctive immuno-regulatory medicament (AIRT). METHODS: The presented real-life retrospective study involved a cohort of 94 adult female patients aged from 30 to 87 years with mean age of 58.4 (SD = 11.37). The cohort was divided into two groups. One group (54 patients; 57.45 %) was treated by using the adjunctive immuno-regulatory medicaments and the other, control group (40 patients; 42.55 %), was without any immunological interventions in relation to secondary immunodeficiency. Patients in both groups were treated by standard oncotherapy. RESULTS: The results show that in patients who were sent for immunological consultation, double-digit values of mild secondary infection frequencies were revealed. When immunologists decided to add adjunctive immunomodulatory medicament, the occurrence of infection and consumption of antibiotics decreased. The decrease was significant in the second evaluated interval (6th - 12th month). CONCLUSIONS: Our results strongly advise regular or even preventive examination of cancer patients by immunologic specialist for the purpose of attenuating some negative consequences of applied anti-tumor therapy (Tab. 1, Fig. 4, Ref. 14). Text in PDF www.elis.sk Keywords: secondary infection, breast cancer, real­life study, clinical immunology, treatment.

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.

"Cytokine storm", not only in COVID-19 patients. Mini-review.

Cytokine storm is a form of uncontrolled systemic inflammatory reaction activated by a variety of factors and leading to a harmful homeostatic process, even to patient's death. Triggers that start the reaction are infection, systemic diseases and rarely anaphylaxis. Cytokine storm is frequently mentioned in connection to medical interventions such as transplantation or administration of drugs. Presented mini-review would like to show current possibilities how to fight or even stop such a life-threatening, immune-mediated process in order to save lives, not only in COVID-19 patients. Early identification of rising state and multilevel course of treatment is imperative. The most widely used molecule for systemic treatment remains tocilizumab. Except for anti IL-6 treatment, contemporary research opens the possibilities for combination of pharmaceutical, non-pharmaceutical and adjunctive treatment in a successful fight with consequences of cytokine storm. Further work is needed to discover the exact signaling pathways that lead to cytokine storm and to determine how these effector molecules and/or combination of processes can help to resolve this frequently fatal episode of inflammation. It is a huge need for all scientists and clinicians to establish a physiological rational for new therapeutic targets that might lead to more personalized medicine approaches.

Determination of immunological stress and oxygen free radical formation in white blood cells during allergen immunotherapy.

BACKGROUND: Airway inflammation represents the basis of respiratory allergic disease and is generally associated with increased oxidative stress. As a consequence of successful treatment leading to hyposenzibilization and remission of symptoms, decrease of reactive oxygen formation is expected. MATERIAL/METHODS: This preliminary study evaluates the production of oxygen free radicals in white blood cells and changes in basic immunological parameters in a cohort of 50 patients (27 females and 23 males, age 14-48 years) with upper airway allergic inflammation caused by pollens, before and during specific immunotherapy. RESULTS: We found an unexpected significant increase in the free radical concentration during and after treatment in comparison to values before the treatment and to the control group. Statistical analysis also found significant increase of IgG3 after initial treatment and also 1 year after allergen immunotherapy. Although there were similar trends in the elevated ROS and elevated IgG3, these were not statistically significant. CONCLUSIONS: We observed changes in oxidative mechanisms in white blood cells of patients treated with AIT. Allergen immunotherapy works at a multilayer level and influences airway inflammation as well as the protective antimicrobial defense in treated patients. Further studies for understanding the mechanisms involved in oxidative stress as well as for laboratory monitoring of therapeutic approaches in allergic diseases are needed.