Janus激酶抑制剂oclacitinib诱导小鼠淋巴组织中T和B细胞的耗竭。

A Jasiecka-Mikołajczyk, T Maślanka
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引用次数: 0

摘要

本研究的主要目的是确定Janus激酶抑制剂奥克拉替尼(OCL)对淋巴组织中CD4+和CD8+T细胞以及B细胞的影响的安全性。小鼠用2.7mg/kg剂量的OCL口服治疗14天,收集外周血、头颈部淋巴结(HNLNs)、纵隔淋巴结(MLNs)和脾脏。研究发现,OCL诱导HNLNs和MLN中CD4+T细胞的耗竭,而它不影响这些组织中CD8+T细胞绝对计数。OCL也导致HNLNs中B细胞的损失,尽管在MLN中没有。此外,OCL耗尽了外周血中的B细胞,但不影响CD4+和CD8+T细胞的绝对计数。因此,可以得出结论,OCL可以诱导对淋巴组织中的CD4+和CD8+T细胞以及B细胞的耗竭作用。这种影响应该被视为一种不利的影响,尤其是在感染患者中。因此,临床意义在于,临床医生应彻底考虑此类患者的获益/风险比。此外,OCL降低了嗜酸性粒细胞、嗜碱性粒细胞、中性粒细胞和单核细胞的绝对计数。然而,由于这些细胞的水平在生理范围内,因此不确定这种影响是否应被视为具有临床重要性。OCL对T和B细胞以及嗜酸性粒细胞和嗜碱性粒细胞的耗竭作用可能有助于该药物在治疗皮肤过敏性疾病中的有益作用。
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Depletion of T and B cells in lymphoid tissues of mice induced by oclacitinib, a Janus kinase inhibitor.

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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