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.
- Publikační typ
- časopisecké články MeSH
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.
V patogenéze prieduškovej astmy a sinonazálnej choroby dôležitú úlohu zohrávajú niektoré cytokíny (IL-4, IL-13, IL-5), ktoré sú v ére biolo-gickej liečby terčom intenzívneho výskumu. Súčasná situácia biologickej liečby alergických foriem refraktérnej astmy prináša viaceré možnosti terapeutického ovplyvnenia. Ako prvá a zároveň najúčinnejšia liečba anti IgE monoklonovou protilátkou (omalizumabom) prináša výrazné zlepšenie funkčných parametrov pľúc, zlepšenie symptomatológie a preukazuje aj výrazný kortikošetriaci efekt. Vzhľadom na individuálnu variabilitu účinnosti liečby vyvinuli sa ďalšie monoklonové protilátky proti IL-4/13 a IL-5 (anti eozinofilová liečba). Naša práca prináša stručný prehľad o úspešnosti liečby bronchiálnej astmy a sinonazálnej choroby jednotlivými monoklonovými protilátkami.
The main role in the pathogenesis of bronchial asthma and sinonasal disease plays some cytokines (IL-4, IL-13, IL-5), which represents a po-tential target for biological treatment. Recent situation in the biological treatment for resistent allergic asthma brings us some new therapeutic options. The first and the most effective treatment with anti-IgE monoclonal antibodies (omalizumab) improves respiratory lung parameters, reduce symptoms and allows the reduction of corticosteroid treatment. Despite of this, due to interindividual variability for treatment response, newer monoclonal antibodies were developed against IL-4/13 and IL-5 (anti-eosinophil therapy). This article brings a short review about the effect of each monoclonal antibodies in treatment of bronchial asthma and sinonasal disease.
- MeSH
- alergická rýma farmakoterapie MeSH
- antiastmatika * farmakologie terapeutické užití MeSH
- biologické markery MeSH
- bronchiální astma * farmakoterapie imunologie patofyziologie MeSH
- cílená molekulární terapie MeSH
- interleukin-13 antagonisté a inhibitory fyziologie MeSH
- interleukin-4 antagonisté a inhibitory fyziologie MeSH
- interleukin-5 antagonisté a inhibitory fyziologie MeSH
- lidé MeSH
- monoklonální protilátky terapeutické užití MeSH
- omalizumab farmakologie terapeutické užití MeSH
- remodelace dýchacích cest účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- abstrakt z konference MeSH
IL-1 sa zúčastňuje regulácie veľkého množstva proinflamatórnych stavov. Z rodiny cytokínu IL-1 kľúčovú úlohu zohráva predovšetkým prozápalový cytokín IL-1β, syntetizovaný v imflamazómoch. Kanakinumab je humánna monoklonálna protilátka proti IL-1β. uplatňuje sa v liečbe autoinflamačných stavov a určitých systémových ochorení spojiva. Z perspektívnych indikácii sa najsľubnejšou javí jeho aplikácia v kontexte aterosklerózy. Hoci v posledných desaťročiach sa viacerými štúdiami potvrdila dôležitosť lipidovej hypotézy, pretrvávajúca prie-merná 40% kardiovaskulárna mortalita naďalej zostáva nad pásmom očakávaného optima. To viedlo v poslednej dobe k ďalším intenzívnym výskumom. V tomto kontexte sa nedávno prezentovali výsledky štúdie CANTOS, prostredníctvom ktorej sa rehabilitovala zápalová hypotéza aterosklerózy. Štúdia CANTOS predstavuje v kontexte zápalovej hypotézy aterosklerózy historický miľník, ktorá otvorila úplne nový prístup k liečbe aterosklerózy – imunomoduláciu.
IL-1 participates in the regulation of many proinflammatory diseases. From the cytokine family of IL-1, the key role in proinflammatory dise-ases is attributed to IL-1β, produced in inflammasomes. Canakinumab is a human monoclonal antibody against IL-1β, applied in the treamtent of many autoinflammatory and systemic connective tissue diseases. Atherosclerosis seems to be the next perspective indication. Despite the outcomes of trials for atherosclerosis in the last decades confirmed the importance of lipid hypotesis, average 40% cardiovascular mortality still remains above the optimal goal. This was the main trigger to initiate new researches in this field. Recently presented outcomes of the CANTOS trial rehabilitated the inflammatory hypothesis of atherosclerosis. CANTOS tial represents in the context of inflammmatory hypothesis of athe-rosclerosis a historic checkpoint, which opened a new approach in the treatment of atherosclerosis – immunomodulation
- Klíčová slova
- kanakinumab, studie CANTOS,
- MeSH
- artritida MeSH
- ateroskleróza diagnóza terapie MeSH
- chronická nemoc terapie MeSH
- imunomodulace MeSH
- interleukin-1beta škodlivé účinky MeSH
- klinická studie jako téma MeSH
- léčivé přípravky MeSH
- lidé MeSH
- protein NLRP3 MeSH
- zánět * terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
