Center of Excellence for Pharmaceutical Sciences, Department of Pharmacology, Faculty of Health Sciences, North-West University, Building G23, Office 315, 11 Hoffman Street, Potchefstroom, 2531, South Africa.
BMC Pharmacol Toxicol. 2024 Aug 19;25(1):52. doi: 10.1186/s40360-024-00778-y.
An increasing body of research implicates inflammatory processes, including alterations in the neutrophil-lymphocyte ratio (NLR), in the pathophysiology of psychiatric illness. The deer mouse (Peromyscus maniculatus bairdii) is commonly studied for its naturalistic expression of compulsive-like behaviour. Towards future efforts to gain an understanding of how innate and adaptive immune processes might be involved in this model, we aimed to study the effects of pegfilgrastim, a pegylated recombinant human granulocyte colony-stimulating factor (g-CSF) analogue, on the NLR of both male and female deer mice.
Briefly, 54 deer mice (equally distributed between sexes) were exposed to a single injection with either control or pegfilgrastim (0.1 or 1 mg/kg) (n = 18 per group). Six mice of each group (three per sex) were euthanized on days two, four and seven post-administration, their blood collected and the NLR calculated. Data were analysed by means of ordinary three-way ANOVA, followed by Bonferroni post-hoc testing.
Irrespective of dose, pegfilgrastim resulted in higher NLR values in mice of both sexes at days four and seven of testing. However, female mice exposed to the higher dose, presented with significantly higher NLR values irrespective of time, compared to male mice exposed to the same.
The data generated from this work highlight important dose- and sex-specific aspects of pegfilgrastim with female mice showing heighted elevation of the NLR in response to high-dose pegfilgrastim administration only. Since the innate immune components of male and female deer mice is differentially sensitive to g-CSF stimulation, our results provide a useful basis for further study of sex-specific immunological processes in deer mice.
越来越多的研究表明炎症过程,包括中性粒细胞与淋巴细胞比值(NLR)的改变,与精神疾病的病理生理学有关。白足鼠(Peromyscus maniculatus bairdii)常因其强迫样行为的自然表达而被研究。为了未来努力了解先天和适应性免疫过程如何参与这种模型,我们旨在研究培非格司亭(一种聚乙二醇化重组人粒细胞集落刺激因子(g-CSF)类似物)对雄性和雌性白足鼠 NLR 的影响。
简要地说,54 只白足鼠(性别均匀分布)接受单次注射对照或培非格司亭(0.1 或 1mg/kg)(每组 18 只)。每组的 6 只小鼠(每性别 3 只)在给药后第 2、4 和 7 天被安乐死,采集血液并计算 NLR。数据通过普通三因素方差分析进行分析,然后进行 Bonferroni 事后检验。
无论剂量如何,培非格司亭在雌雄小鼠的第 4 和第 7 天均导致 NLR 值升高。然而,暴露于较高剂量的雌性小鼠在任何时间点的 NLR 值均显著高于暴露于相同剂量的雄性小鼠。
这项工作产生的数据突出了培非格司亭在剂量和性别方面的重要方面,雌性小鼠对高剂量培非格司亭给药的 NLR 升高更为明显。由于雄性和雌性白足鼠的先天免疫成分对 g-CSF 刺激的敏感性不同,我们的结果为进一步研究白足鼠的性别特异性免疫过程提供了有用的基础。