{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T13:46:29Z","timestamp":1776951989732,"version":"3.51.4"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T00:00:00Z","timestamp":1724025600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T00:00:00Z","timestamp":1724025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005274","name":"North-West University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005274","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pharmacol Toxicol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>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 <jats:italic>(Peromyscus maniculatus bairdii)<\/jats:italic> 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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Briefly, 54 deer mice (equally distributed between sexes) were exposed to a single injection with either control or pegfilgrastim (0.1 or 1\u00a0mg\/kg) (<jats:italic>n<\/jats:italic>\u2009=\u200918 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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>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.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40360-024-00778-y","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T10:02:57Z","timestamp":1724061777000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Differential impact of pegfilgrastim, a recombinant human granulocyte colony stimulating factor, on the neutrophil count of male and female deer mice (Peromyscus maniculatus bairdii)"],"prefix":"10.1186","volume":"25","author":[{"given":"J.P.","family":"Strydom","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Brand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francois P.","family":"Viljoen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"De Wet","family":"Wolmarans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,8,19]]},"reference":[{"issue":"6","key":"778_CR1","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/s41582-019-0174-4","volume":"15","author":"K Pape","year":"2019","unstructured":"Pape K, Tamouza R, Leboyer M, Zipp F. Immunoneuropsychiatry\u2014novel perspectives on brain disorders. Nat Rev Neurol. 2019;15(6):317\u201328.","journal-title":"Nat Rev Neurol"},{"key":"778_CR2","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.jpsychires.2021.01.022","volume":"135","author":"M Thienemann","year":"2021","unstructured":"Thienemann M, Park M, Chan A, Frankovich J. Patients with abrupt early-onset OCD due to PANS tolerate lower doses of antidepressants and antipsychotics. J Psychiatr Res. 2021;135:270\u201378.","journal-title":"J Psychiatr Res"},{"issue":"3","key":"778_CR3","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1016\/j.psychres.2015.07.009","volume":"229","author":"NP Rao","year":"2015","unstructured":"Rao NP, Venkatasubramanian G, Ravi V, Kalmady S, Cherian A, Yc JR. Plasma cytokine abnormalities in drug-na\u00efve, comorbidity-free obsessive\u2013compulsive disorder. Psychiatry Res. 2015;229(3):949\u201352.","journal-title":"Psychiatry Res"},{"issue":"7","key":"778_CR4","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1016\/j.psyneuen.2003.08.008","volume":"29","author":"D Denys","year":"2004","unstructured":"Denys D, Fluitman S, Kavelaars A, Heijnen C, Westenberg H. Decreased TNF-\u03b1 and NK activity in obsessive-compulsive disorder. Psychoneuroendocrinology. 2004;29(7):945\u201352.","journal-title":"Psychoneuroendocrinology"},{"issue":"7","key":"778_CR5","doi-asserted-by":"publisher","first-page":"4751","DOI":"10.1007\/s12035-018-1409-x","volume":"56","author":"TD Cosco","year":"2019","unstructured":"Cosco TD, Pillinger T, Emam H, Solmi M, Budhdeo S, Prina AM, et al. Immune aberrations in obsessive-compulsive disorder: a systematic review and meta-analysis. Mol Neurobiol. 2019;56(7):4751\u201359.","journal-title":"Mol Neurobiol"},{"issue":"7","key":"778_CR6","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1089\/cap.2016.0148","volume":"27","author":"J Frankovich","year":"2017","unstructured":"Frankovich J, Swedo S, Murphy T, Dale RC, Agalliu D, Williams K, et al. Clinical management of pediatric acute-onset neuropsychiatric syndrome: part II\u2014use of immunomodulatory therapies. J Child Adolesc Psychopharmacol. 2017;27(7):574\u201393.","journal-title":"J Child Adolesc Psychopharmacol"},{"issue":"2","key":"778_CR7","doi-asserted-by":"publisher","first-page":"e25","DOI":"10.1192\/bjo.2019.10","volume":"5","author":"E Hesselmark","year":"2019","unstructured":"Hesselmark E, Bejerot S. Clinical features of paediatric acute-onset neuropsychiatric syndrome: findings from a case\u2013control study. BJPsych Open. 2019;5(2):e25.","journal-title":"BJPsych Open"},{"key":"778_CR8","doi-asserted-by":"crossref","unstructured":"Bhikram T, Sandor P. Neutrophil-lymphocyte ratios as inflammatory biomarkers in psychiatric patients. Brain Behav Immun. 2022.","DOI":"10.1016\/j.bbi.2022.07.006"},{"issue":"3","key":"778_CR9","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/j.ajem.2019.10.023","volume":"38","author":"Z Huang","year":"2020","unstructured":"Huang Z, Fu Z, Huang W, Huang K. Prognostic value of neutrophil-to-lymphocyte ratio in sepsis: a meta-analysis. Am J Emerg Med. 2020;38(3):641\u201347.","journal-title":"Am J Emerg Med"},{"key":"778_CR10","doi-asserted-by":"crossref","unstructured":"Kong W, He Y, Bao H, Zhang W, Wang X. Diagnostic value of neutrophil-lymphocyte ratio for predicting the severity of acute pancreatitis: a meta-analysis. Dis Markers. 2020;2020.","DOI":"10.1155\/2020\/9731854"},{"key":"778_CR11","doi-asserted-by":"crossref","unstructured":"Faria SS, Fernandes Jr PC, Silva MJB, Lima VC, Fontes W, Freitas-Junior R, et al. The neutrophil-to-lymphocyte ratio: a narrative review. Ecancermedicalscience. 2016;10.","DOI":"10.3332\/ecancer.2016.702"},{"key":"778_CR12","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.psychres.2018.12.131","volume":"272","author":"G \u00d6zyurt","year":"2019","unstructured":"\u00d6zyurt G, Binici NC. The neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in adolescent obsessive-compulsive disorder: does comorbid anxiety disorder affect inflammatory response? Psychiatry Res. 2019;272:311\u201315.","journal-title":"Psychiatry Res"},{"issue":"1","key":"778_CR13","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.neubiorev.2011.04.006","volume":"36","author":"N Albelda","year":"2012","unstructured":"Albelda N, Joel D. Animal models of obsessive-compulsive disorder: exploring pharmacology and neural substrates. Neurosci Biobehav Rev. 2012;36(1):47\u201363.","journal-title":"Neurosci Biobehav Rev"},{"issue":"0","key":"778_CR14","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.bbr.2013.08.049","volume":"256","author":"DW Wolmarans","year":"2013","unstructured":"Wolmarans DW, Brand L, Stein DJ, Harvey BH. Reappraisal of spontaneous stereotypy in the deer mouse as an animal model of obsessive-compulsive disorder (OCD): response to escitalopram treatment and basal serotonin transporter (SERT) density. Behav Brain Res. 2013;256(0):545\u201353.","journal-title":"Behav Brain Res"},{"issue":"2","key":"778_CR15","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1007\/s11011-017-0161-7","volume":"33","author":"IM Scheepers","year":"2018","unstructured":"Scheepers IM, Stein DJ, Harvey BH. Peromyscus maniculatus bairdii as a naturalistic mammalian model of obsessive-compulsive disorder: current status and future challenges. Metab Brain Dis. 2018;33(2):443\u201355.","journal-title":"Metab Brain Dis"},{"issue":"4","key":"778_CR16","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1097\/FBP.0000000000000678","volume":"33","author":"M de Ridder","year":"2022","unstructured":"de Ridder M, Mograbi D, Wolmarans DW. Spontaneous alternation and stereotypical behaviour in deer mice: response to escitalopram and levetiracetam. Behav Pharmacol. 2022;33(4):282\u201390.","journal-title":"Behav Pharmacol"},{"issue":"2","key":"778_CR17","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.bbr.2004.08.003","volume":"157","author":"MF Presti","year":"2005","unstructured":"Presti MF, Lewis MH. Striatal opioid peptide content in an animal model of spontaneous stereotypic behavior. Behav Brain Res. 2005;157(2):363\u201368.","journal-title":"Behav Brain Res"},{"key":"778_CR18","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1007\/s003600050161","volume":"168","author":"G Demas","year":"1998","unstructured":"Demas G, Nelson R. Short-day enhancement of immune function is independent of steroid hormones in deer mice (Peromyscus maniculatus). J Comp Physiol B. 1998;168:419\u201326.","journal-title":"J Comp Physiol B"},{"key":"778_CR19","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.2165\/00003495-200262080-00012","volume":"62","author":"MP Curran","year":"2002","unstructured":"Curran MP, Goa KL. Pegfilgrastim. Drugs. 2002;62:1207\u201313.","journal-title":"Drugs"},{"issue":"12","key":"778_CR20","doi-asserted-by":"publisher","first-page":"1724","DOI":"10.1016\/S0301-472X(99)00112-5","volume":"27","author":"G Molineux","year":"1999","unstructured":"Molineux G, Kinstler O, Briddell B, Hartley C, McElroy P, Kerzic P, et al. A new form of Filgrastim with sustained duration in vivo and enhanced ability to mobilize PBPC in both mice and humans. Exp Hematol. 1999;27(12):1724\u201334.","journal-title":"Exp Hematol"},{"issue":"7","key":"778_CR21","first-page":"2085","volume":"7","author":"BI Lord","year":"2001","unstructured":"Lord BI, Woolford LB, Molineux G. Kinetics of neutrophil production in normal and neutropenic animals during the response to filgrastim (r-metHu G-CSF) or filgrastim SD\/01 (PEG-r-metHu G-CSF). Clin Cancer Res. 2001;7(7):2085\u201390.","journal-title":"Clin Cancer Res"},{"issue":"30","key":"778_CR22","first-page":"2020","volume":"2013","author":"W Underwood","year":"2020","unstructured":"Underwood W, Anthony R. AVMA guidelines for the euthanasia of animals: 2020 edition. Retrieved on March. 2020;2013(30):2020\u201321.","journal-title":"Retrieved on March"},{"issue":"1","key":"778_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0272-2712(03)00064-7","volume":"22","author":"B Houwen","year":"2002","unstructured":"Houwen B. Blood film preparation and staining procedures. Clin Lab Med. 2002;22(1):1\u201314.","journal-title":"Clin Lab Med"},{"issue":"6","key":"778_CR24","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1093\/labmed\/11.6.371","volume":"11","author":"JA Koepke","year":"1980","unstructured":"Koepke JA. Standardization of the manual differential leukocyte count. Lab Med. 1980;11(6):371\u201375.","journal-title":"Lab Med"},{"key":"778_CR25","volume-title":"The Neutrophil-to-lymphocyte Ratio in the Deer Mouse and Its Response to Escitalopram Treatment","author":"M Meiring","year":"2021","unstructured":"Meiring M. The Neutrophil-to-lymphocyte Ratio in the Deer Mouse and Its Response to Escitalopram Treatment. Potchefstroom: North-West University; 2021."},{"key":"778_CR26","first-page":"2","volume-title":"Statistical power analysis for the behavioral sciences","author":"J Cohen","year":"1988","unstructured":"Cohen J. Statistical power analysis for the behavioral sciences. Hillsdale, NJ: L. Lawrence Earlbaum Associates; 1988, p. 2."},{"issue":"7","key":"778_CR27","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/laban.1298","volume":"46","author":"DL Hickman","year":"2017","unstructured":"Hickman DL. Evaluation of the neutrophil: lymphocyte ratio as an indicator of chronic distress in the laboratory mouse. Lab Animal. 2017;46(7):303\u201307.","journal-title":"Lab Animal"},{"issue":"14","key":"778_CR28","first-page":"3710","volume":"51","author":"H Tanaka","year":"1991","unstructured":"Tanaka H, Satake-Ishikawa R, Ishikawa M, Matsuki S, Asano K. Pharmacokinetics of recombinant human granulocyte colony-stimulating factor conjugated to polyethylene glycol in rats. Cancer Res. 1991;51(14):3710\u201314.","journal-title":"Cancer Res"},{"issue":"6","key":"778_CR29","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1111\/j.1365-2184.2009.00638.x","volume":"42","author":"M Scholz","year":"2009","unstructured":"Scholz M, Ackermann M, Engel C, Emmrich F, Loeffler M, Kamprad M. A pharmacokinetic model of filgrastim and pegfilgrastim application in normal mice and those with cyclophosphamide-induced granulocytopaenia. Cell Prolif. 2009;42(6):813\u201322.","journal-title":"Cell Prolif"},{"issue":"4","key":"778_CR30","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1053\/cp.1999.v66.a101210","volume":"66","author":"T Hartung","year":"1999","unstructured":"Hartung T, Doecke WD, Bundschuh D, Foote M, Gantner F, Hermann C, et al. Effect of filgrastim treatment on inflammatory cytokines and lymphocyte functions. Clin Pharm Therap. 1999;66(4):415\u201324.","journal-title":"Clin Pharm Therap"},{"key":"778_CR31","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s40259-015-0127-4","volume":"29","author":"T Arvedson","year":"2015","unstructured":"Arvedson T, O\u2019Kelly J, Yang B-B. Design rationale and development approach for pegfilgrastim as a long-acting granulocyte colony-stimulating factor. BioDrugs. 2015;29:185\u201398.","journal-title":"BioDrugs"},{"issue":"1","key":"778_CR32","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1111\/brv.12243","volume":"92","author":"YZ Foo","year":"2017","unstructured":"Foo YZ, Nakagawa S, Rhodes G, Simmons LW. The effects of sex hormones on immune function: a meta-analysis. Biol Rev. 2017;92(1):551\u201371.","journal-title":"Biol Rev"},{"key":"778_CR33","doi-asserted-by":"crossref","unstructured":"De Brouwer G, Engelbrecht J, Mograbi D, Legoabe LJ, Steyn S, Wolmarans DW. Stereotypy and spontaneous alternation in deer mice and its response to anti-adenosinergic intervention. J Neurosci Res. 2021;In Press.","DOI":"10.1002\/jnr.24867"}],"container-title":["BMC Pharmacology and Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40360-024-00778-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40360-024-00778-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40360-024-00778-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T10:11:47Z","timestamp":1724062307000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcpharmacoltoxicol.biomedcentral.com\/articles\/10.1186\/s40360-024-00778-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,19]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["778"],"URL":"https:\/\/doi.org\/10.1186\/s40360-024-00778-y","relation":{},"ISSN":["2050-6511"],"issn-type":[{"value":"2050-6511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,19]]},"assertion":[{"value":"12 April 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 August 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This work was approved the North-West University Animal Research Ethics Committee (approval number: NWU-760-22-A5). This formed part of the M.Sc. project of J.P.S. at the NWU.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"52"}}