Differential impact of pegfilgrastim, a recombinant human granulocyte colony stimulating factor, on the neutrophil count of male and female deer mice (Peromyscus maniculatus bairdii)

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Animal model; Compulsive; Deer mouse; G-CSF; Neutrophil-lymphocyte ratio; Pegfilgrastim.

Fig. 1

Schematic representation of experimental layout. s.c.i.: subcutaneous injection; crosses indicate euthanisation of six animals per group on days 2, 4, and 7, respectively

Fig. 2

NLR values of male and female deer mice exposed to a single s.c.i with either control or pegfilgrastim (0.1 and 1 mg/kg) as calculated at two, four, and seven days post injection. Data are reflective of individual mice, with lines indicating mean ± standard deviation. Only the main effects of dose at day four and seven are shown. All other descriptive statistics are provided in Table 2. Three-way ANOVA followed by Bonferroni. p ≤ 0.004. NLR neutrophil-lymphocyte ratio