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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
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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

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