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Depletion of T and B cells in lymphoid tissues of mice induced by oclacitinib, a Janus kinase inhibitor

A. Jasiecka-Mikołajczyk T. Maślanka
Polish Journal of Veterinary Sciences | 2023 | vol. 26 | No 3 | 431–440 | DOI: 10.24425/pjvs.2023.145049
Keywords B cells CD4+ T cells CD8+ T cells Janus kinase inhibitor lymphoid tissue oclacitinib
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Abstract

The main purpose of the study was to determine the safety of oclacitinib (OCL), a Janus kinase inhibitor, with respect of its effect on CD4 + and CD8 + T cells as well as B cells in the lymphoid tissue. The mice were treated orally with OCL at a dose of 2.7 mg/kg for 14 days and peripheral blood, head and neck lymph nodes (HNLNs), mediastinal lymph nodes (MLNs) and spleen were collected. The study found that OCL induced depletion of CD4 + T cells in the HNLNs and MLNs, while it did not affect the absolute count of CD8 + T cells in these tissues. Also OCL caused a loss of B cells in the HNLNs, although not in the MLNs. Moreover, OCL depleted B cells in the peripheral blood, but did not affect the absolute count of CD4 + and CD8 + T cells. Thus, it can be concluded that OCL may induce a depletive effect on CD4 + and CD8 + T cells as well as B cells in the lymphoid tissue. This effect should be seen as an unfavorable one, especially in patients with infections. Therefore, a clinical implication is that in such patients, the benefit/risk ratio should be thoroughly considered by clinicians. Moreover, OCL reduced the absolute count of eosinophils, basophils, neutrophils and monocytes. However, it is uncertain whether this effect should be considered to be of clinical importance because the levels of these cells were within the physiological range. It is possible that the depletive effect of OCL toward T and B cells, as well as eosinophils and basophils may contribute to the beneficial effects of the drug in the treatment of skin allergic diseases.
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Authors and Affiliations

A. Jasiecka-Mikołajczyk
1
T. Maślanka
1
  1. Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego 13, 10-718 Olsztyn, Poland

Teriflunomide induces Foxp3 expression in murine CD8 + T cells while IL-27 and retinoic acid exert a synergistic effect on the induction of CD39 expression on these cells

T. Maślanka A. Jasiecka-Mikołajczyk
Polish Journal of Veterinary Sciences | 2023 | vol. 26 | No 4 | 591-609 | DOI: 10.24425/pjvs.2023.148279
Keywords CD8+ T cells Treg cells Foxp3 IL-27 ATRA teriflunomide
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Abstract

The purpose of this study was to verify the possibility of pharmacological induction of Foxp3 +CD25 +CD8 + and Foxp3 -CD103 +CD8 + T regulatory cells ‘armed’ with immunosuppressive molecules, i.e. CD39 and IL-10. To achieve this purpose, stimulated and unstimulated murine lymphocytes were exposed to IL-27, teriflunomide (TER) and all trans retinoic acid (ATRA). The study found that: (a) IL-27 induced CD39 expression on Foxp3 +CD25 +CD8 + T cells and the ability of CD103+Foxp3-CD8+ T cells to produce IL-10 as well as increasing the absolute number of IL-10 +CD103 +Foxp3 -CD8 + T cells; (b) TER induced Foxp3 expression in CD25+CD8+ T cells and CD103 expression on Foxp3 -CD8 + T cells as well as increasing the absolute number of Foxp3 +CD25 +CD8 + T cells; (c) ATRA induced the capacity of Foxp3 +CD25 +CD8 + T cells to produce IL-10. The following desired interactions were demonstrated between IL-27 and ATRA: (a) a strong synergistic effect with respect to increasing CD39 expression and the ability to produce IL-10 by Foxp3 +CD25 +CD8 + T cells; (b) a synergistic effect with respect to increasing the absolute count of CD39 +Foxp3 +CD25 +CD8 + T cells. The study revealed that TER abolished all these effects. Therefore, a combination of the tested agents did not induce the generation of Foxp3 +CD25 +CD8 + and Foxp3 -CD103+CD8+ T cells characterized by extensive CD39 expression and IL-10 production. Thus, in the context of the pharmacological induction of IL-10 +CD39 +Foxp3 +CD25 +CD8 + and IL-10 +CD103 +Foxp3 -CD8 + T cells, these findings strongly suggest that a combination of TER with IL-27 and/or ATRA does not provide any benefits over TER alone; moreover, such a combination may result in abolishing the desired effects exerted by IL-27 and/or ATRA.
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Authors and Affiliations

T. Maślanka
1
A. Jasiecka-Mikołajczyk
1
  1. Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego 13, 10-718 Olsztyn, Poland

Determination of tigecycline in turkey plasma by LC-MS/MS: validation and application in a pharmacokinetic study

A. Jasiecka-Mikołajczyk J.J. Jaroszewski
Polish Journal of Veterinary Sciences | 2017 | No 2 | DOI: 10.1515/pjvs-2017-0029
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Authors and Affiliations

A. Jasiecka-Mikołajczyk
J.J. Jaroszewski

Effect of tigecycline on the production of selected cytokines and counts of murine CD4+ and CD8+ T cells - an in vitro study

A. Jasiecka-Mikołajczyk J.J. Jaroszewski T. Maślanka
Polish Journal of Veterinary Sciences | 2018 | vol. 21 | No 4 | 819-822 | DOI: 10.24425/pjvs.2018.125594
Keywords tigecycline CD4+ T cells CD8+ T cells cytokines mouse
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Abstract

Due to the unrecognized effect of tigecycline (TIG) on CD4+ and CD8+ T cells, the present study has been undertaken in order to determine whether the drug can affect these cells in respect of their counts, and the production of IFN-γ, IL-17 (pro-inflammatory and immune-protective cytokines), IL-4 (anti-inflammatory and immune-protective cytokine), IL-10 and TGF-β (anti-inflammatory and immune-suppressive cytokines). Murine lymphocytes were treated with TIG for 48 and 96 h at concentrations reflecting its plasma levels obtained in vivo at therapeutic doses, and at 10-fold lower concentrations. It was found that TIG neither affected substantially the percentage and absolute counts of entire CD4+ and CD8+ T cell populations nor influenced the Foxp3+CD25+CD4+ regulatory/suppressive T cell subset. Furthermore, the percentages of IL-4-, IL-10-, IL-17- and TGF-β-producing CD4+ T cells were not altered following the exposure to TIG. Similarly, TIG did not influence IFN-γ production by CD8+ T cells. Thus, with respect to the parameters evaluated, TIG does not seem to exert immune-suppressive and anti-inflammatory effects.

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Authors and Affiliations

A. Jasiecka-Mikołajczyk
J.J. Jaroszewski
T. Maślanka

Differences in the pharmacokinetics of flumequine after single and continuous oral administration in non-fasted broiler chickens

H. Madej-Śmiechowska A. Orzoł A. Jasiecka-Mikołajczyk H. Ziółkowski J.J. Jaroszewski
Polish Journal of Veterinary Sciences | 2018 | vol. 21 | No 3 | 631–634 | DOI: 10.24425/124298
Keywords flumequine HPLC interactions with feed broiler chickens
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Abstract

The aim of this study was to determine the influence of feed on the pharmacokinetics of flumequine (FLU) administered to broiler chickens as follows: directly into the crop (10 mg/kg of BW) of fasted (group I/control) and non-fasted chickens (group II), or administered continu- ously with drinking water (1 g/L for 72 h) and with unlimited access to feed (group III). Plasma concentration of FLU was determined by high-performance liquid chromatography with fluo- rescence detection. In group II, a significant decrease in the maximum concentration (Cmax = 2.13±0.7 μg/mL) and the area under the concentration curve from zero to infinity (AUC0→∞ = 7.47±2.41 μg·h/mL) was noted as compared to the control group (Cmax = 4.11±1.68 μg/mL and AUC0→∞ = 18.17±6.85 μg·h/mL, respectively). In group III, the decrease in AUC was signifi- cant only in the first 3 hours (AUC0→3 = 5.02±1.34 μg·h/mL) as compared to the control group (AUC0→3 = 7.79±3.29 μg·h/mL). The results indicate that feed reduced the bioavailability of FLU from the gastrointestinal tract by at least 50% after the administration of a single oral dose. However, continuous administration of FLU with drinking water could compensate for the feed-induced decrease in absorption after single oral dose.

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Authors and Affiliations

H. Madej-Śmiechowska
A. Orzoł
A. Jasiecka-Mikołajczyk
H. Ziółkowski
J.J. Jaroszewski

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