{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:34:05Z","timestamp":1790573645313,"version":"4.1.0"},"reference-count":90,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,4,3]],"date-time":"2022-04-03T00:00:00Z","timestamp":1648944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5T35OD010432"],"award-info":[{"award-number":["5T35OD010432"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM103646"],"award-info":[{"award-number":["P20GM103646"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Disease or trauma of orthopedic tissues, including osteomyelitis, osteoporosis, arthritis, and fracture, results in a complex immune response, leading to a change in the concentration and milieu of immunological cells and proteins in the blood. While C\u2010reactive protein levels and white blood cell counts are used to track inflammation and infection clinically, controlled longitudinal studies of disease\/injury progression are limited. Thus, the use of clinically\u2010relevant animal models can enable a more in\u2010depth understanding of disease\/injury progression and treatment efficacy. Though longitudinal tracking of immunological markers has been performed in rat models of various inflammatory and infectious diseases, currently there is no consensus on which markers are sensitive and reliable for tracking levels of inflammation and\/or infection. Here, we discuss the blood markers that are most consistent with other outcome measures of the immune response in the rat, by reviewing their utility for longitudinal tracking of infection and\/or inflammation in the following types of models: localized inflammation\/arthritis, injury, infection, and injury\u2009+\u2009infection. While cytokines and acute phase proteins such as haptoglobin, fibrinogen, and \u03b1<jats:sub>2<\/jats:sub>\u2010macroglobulin demonstrate utility for tracking immunological response in many inflammation and infection models, there is likely not a singular superior marker for all rat models. Instead, longitudinal characterization of these models may benefit from evaluation of a collection of cytokines and\/or acute phase proteins. Identification of immunological plasma markers indicative of the progression of a pathology will allow for the refinement of animal models for understanding, diagnosing, and treating inflammatory and infectious diseases of orthopedic tissues.<\/jats:p>","DOI":"10.1002\/jor.25330","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T03:09:24Z","timestamp":1647918564000},"page":"1251-1262","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Review of immunological plasma markers for longitudinal analysis of inflammation and infection in rat models"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1413-9842","authenticated-orcid":false,"given":"Malley A.","family":"Gautreaux","sequence":"first","affiliation":[{"name":"Department of Agricultural and Biological Engineering Mississippi State University Mississippi State Mississippi USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9226-385X","authenticated-orcid":false,"given":"Luke J.","family":"Tucker","sequence":"additional","affiliation":[{"name":"Department of Agricultural and Biological Engineering Mississippi State University Mississippi State Mississippi USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier J.","family":"Person","sequence":"additional","affiliation":[{"name":"Department of Agricultural and Biological Engineering Mississippi State University Mississippi State Mississippi USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haley K.","family":"Zetterholm","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Mississippi State University Mississippi State Mississippi USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4156-7586","authenticated-orcid":false,"given":"Lauren B.","family":"Priddy","sequence":"additional","affiliation":[{"name":"Department of Agricultural and Biological Engineering Mississippi State University Mississippi State Mississippi USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,4,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60687-5"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2017889118"},{"key":"e_1_2_9_4_1","first-page":"517","article-title":"Acute phase response in animals: a review","volume":"59","author":"Cray C","year":"2009","journal-title":"Comp Med"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ame2.12149"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24689"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0162-3109(86)90026-3"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00776-006-1026-9"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1258\/002367793781082412"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/ilar.31.4.5"},{"key":"e_1_2_9_11_1","first-page":"169","article-title":"Observations on the delay in onset of the acute phase protein response","volume":"69","author":"Myers MA","year":"1988","journal-title":"Br J Exp Pathol"},{"key":"e_1_2_9_12_1","article-title":"Acute phase protein levels in rats with experimentally induced infectious and noninfectious inflammation","volume":"4","author":"Abbak M","year":"2017","journal-title":"Dairy Vet Sci J"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01974928"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199902113400607"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arth.2012.03.059"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v042a21"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0227748"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.07.040"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.651619"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.L.01654"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-015-4354-2"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.20.00029"},{"key":"e_1_2_9_23_1","first-page":"55","article-title":"Isolation and characterization of C\u2010reactive protein and serum amyloid P component in the rat","volume":"45","author":"Beer FC","year":"1982","journal-title":"Immunology"},{"key":"e_1_2_9_24_1","first-page":"332","article-title":"Variation of serum \u03b1 2\u2010macroglobulin concentration in healthy rats and rats inoculated with staphylococcus aureus or subjected to surgery","volume":"51","author":"Jinbo T","year":"2001","journal-title":"Comp Med"},{"key":"e_1_2_9_25_1","first-page":"392","article-title":"Markers of experimental acute inflammation in the Wistar Han rat with particular reference to haptoglobin and C\u2010reactive protein","volume":"77","author":"Giffen PS","year":"2003","journal-title":"Arch. Toxicol. 2003 777"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00580-018-2713-6"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40744-020-00217-4"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199910)42:10<2060::AID-ANR6>3.0.CO;2-L"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/009841096161564"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01927730"},{"key":"e_1_2_9_31_1","first-page":"26","article-title":"A simple inflammation model that distinguishes between the actions of anti\u2010inflammatory and anti\u2010rheumatic drugs","volume":"47","author":"Lewis EJ","year":"1998","journal-title":"Inflamm. Res. 1998 471"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2795(81)90033-7"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1258\/0023677021912433"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1258\/la.2009.009042"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1258\/la.2011.010112"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2427(97)00062-7"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1631\/jzus.2005.B1045"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(94)90138-4"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e31823918c2"},{"key":"e_1_2_9_40_1","first-page":"119","article-title":"Comparative clinical study of protein SAP (amyloid P component) and C\u2010reactive protein in serum","volume":"32","author":"Pepys MB","year":"1978","journal-title":"Clin Exp Immunol"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-019-1386-4"},{"key":"e_1_2_9_42_1","first-page":"528","article-title":"Inflammatory response markers in rats undergoing abdominal surgical procedures","volume":"33","author":"Kirdak T","year":"2020","journal-title":"Ann Gastroenterol"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jksus.2020.03.035"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.02.015"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301539"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj1590643"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.85B6.13509"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-020-01618-5"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00402-016-2419-7"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-014-2582-9"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0220421"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24556"},{"key":"e_1_2_9_53_1","first-page":"3060","article-title":"Masquelet induced membrane technique for treatment of rat chronic osteomyelitis","volume":"16","author":"Cui T","year":"2018","journal-title":"Exp Ther Med"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1242\/bio.045203"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2019.07.45"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.b.10051"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-016-1005-z"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.120405"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0BM01728K"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1538\/expanim.59.589"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)47149-4"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4800(92)90023-5"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1515\/bmc-2018-0007"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0603252"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.06.033"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.181845"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2005.03.004"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/0952-7915(92)90082-P"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.4.1491"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2427(96)05698-X"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2650621"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1515\/acve-2015-0013"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2012.04.004"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4838(00)00153-9"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1051\/vetres:2004002"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840080234"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1982.tb22124.x"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1982.tb22140.x"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200318921"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1128\/CDLI.10.4.652-657.2003"},{"key":"e_1_2_9_81_1","first-page":"647","article-title":"Biological functions of haptoglobin\u2014new pieces to an old puzzle","volume":"35","author":"Dobryszycka W","year":"1997","journal-title":"Clin Chem Lab Med"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7036344"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510847103"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03104"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.46867\/IJCP.2007.20.02.15"},{"key":"e_1_2_9_86_1","first-page":"181","article-title":"Effect of various physical stress models on serum cortisol level in Wistar Rats","volume":"8","author":"Jameel MK","year":"2014","journal-title":"J Clin Diagn Res"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00744-06"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1080\/713609210"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02382"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1155\/S0962935192000085"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI103579"}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.25330","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jor.25330","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.25330","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T09:01:52Z","timestamp":1692954112000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.25330"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,3]]},"references-count":90,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["10.1002\/jor.25330"],"URL":"https:\/\/doi.org\/10.1002\/jor.25330","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,3]]},"assertion":[{"value":"2021-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}