Longitudinal Baboon (Papio anubis) Neutrophil to Lymphocyte Ratio (NLR), and Correlations with Monthly Sedation Rate and Within-Group Sedation Order

Abstract

Neutrophil to lymphocyte ratio (NLR) is a simple marker of stress and inflammation, but there is limited research regarding NLR in nonhuman primates (NHPs), with studies showing associations with longevity, certain medical conditions, and stressful circumstances. Here, we examined baboon NLR longitudinally, and as a function of health parameters. We also examined whether NLR was affected by sedation rate, as well as the order of sedation within a group, given that sedation events during clinical and research practices can induce stress in NHPs. While older adult and geriatric baboon NLR did not differ longitudinally, juvenile and young adult NLR tended to increase, primarily driven by increases in females. Additionally, baboons sedated later within a group showed significantly higher NLRs than those sedated earlier in the process. However, baboons with higher sedation rates per month showed lower NLRs. These data indicate that NLR may be dysregulated in different ways as a function of different types of stress, with sedation order (i.e., acute stress) causing pathological increases in NLR, and sedation rate over time (i.e., chronic stress) causing decreases. Importantly, we propose that NLR, a routinely obtained veterinary measure, has potential utility as a welfare indicator of stress resulting from clinical and research practices, as well as a measure that can inform behavioral management practices and interventions.

Keywords: immune dysregulation; nonhuman primate; stress; welfare.

Figure 1

NLR across timepoints 1 through 5. Panel (A): collapsed across sex and rearing, with a significant effect of time but pairwise comparisons were not significant (p > 0.11); (B): trending effect of sex (p = 0.10); (C): significant main effect of rearing (p < 0.05): mother-reared (MR), nursery-reared (NR). Log10 refers to the log-transformed NLR variable.

Figure 2

Relationship between NLR and age across the entire sample. Log10 refers to the log-transformed NLR variable.

Figure 3

Relationship between sedation rate per month and NLR across baboons who were on study and control baboons who were matched on age, sex, and rearing. Control baboons (black trendline) showed no relationship between NLR and sedation rate, while study baboons (gray trendline) showed a significant negative relationship. Log10 refers to the log-transformed NLR variable. The dotted line indicates zero.

Figure 4

(A) The percentage of each age category showing increases (≥1 ratio unit increase), decreases (≥1 ratio unit decrease), or no change (0 ± 0.99 ratio unit change) in NLR over time. (B) Box-and-whisker plots showing change scores across age categories and sex. (C) Average change scores (NLR at first timepoint minus NLR at most recent timepoint) across age groups, showing that NLR increased over time in juvenile and young adults, but decreased over time for geriatric baboons. (D) Females tend to drive the increases found in juveniles and young adults over time, and the two only males tend to drive the decreases in geriatric baboons. M: males; F: females. NLR change scores based on raw NLR data for each baboon.

Figure 5

The linear relationship between NLR (log 10 transformed) and sedation order across males and females. Log10 refers to the log-transformed NLR variable.

Figure 6

(A): Differences in mean NLR (log 10 transformed) as a function of sex and presence of an injury. (B): Differences in mean NLR (log 10 transformed) as a function of rearing and presence of a dependent infant (i.e., infant younger than 6 months of age). MR: mother-reared, NR: nursery-reared.