{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:27:42Z","timestamp":1791473262472,"version":"4.3.4"},"reference-count":45,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T00:00:00Z","timestamp":1697673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Royal Physiographic Society in Lund, Sweden"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system caused by myelin-specific autoreactive T cells. We previously demonstrated intestinal barrier disruption and signs of inflammation in experimental autoimmune encephalomyelitis (EAE), a model of MS. Fecal calprotectin is a disease activity biomarker in inflammatory bowel diseases, released by neutrophils in response to inflammation. We aimed to further investigate EAE manifestations in the gastrointestinal tract and to determine whether calprotectin is a useful biomarker of intestinal inflammation in EAE. Calprotectin was analyzed in feces, cecal contents, and plasma of EAE mice. Infiltrating neutrophils and goblet cells were investigated in different parts of the gastrointestinal tract before the onset of neurological symptoms and during established disease. We found increased calprotectin levels in feces, cecal content, and plasma preceding EAE onset that further escalated during disease progression. Increased neutrophil infiltration in the intestinal tissue concomitant with IL-17 expression and myeloperoxidase activity was found to correlate well with clinical activity. Increased goblet cells in the intestine, similar to irritable bowel syndrome (IBS), were also observed. The results suggest calprotectin as a good biomarker of gastrointestinal inflammation in EAE and the potential of this model as a useful animal model for IBS.<\/jats:p>","DOI":"10.3390\/ijms242015367","type":"journal-article","created":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T07:15:36Z","timestamp":1697699736000},"page":"15367","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Elevated Fecal Calprotectin Accompanied by Intestinal Neutrophil Infiltration and Goblet Cell Hyperplasia in a Murine Model of Multiple Sclerosis"],"prefix":"10.3390","volume":"24","author":[{"given":"Mehrnaz","family":"Nouri","sequence":"first","affiliation":[{"name":"ImmuneBiotech AB, Medicon Village, 223 63 Lund, Sweden"},{"name":"Department of Biology, Lund University, 223 62 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9296-2845","authenticated-orcid":false,"given":"Bj\u00f6rn","family":"Westr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Biology, Lund University, 223 62 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahram","family":"Lavasani","sequence":"additional","affiliation":[{"name":"ImmuneBiotech AB, Medicon Village, 223 63 Lund, Sweden"},{"name":"Department of Clinical Sciences Lund, Lund University, 221 85 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1212\/CPJ.0000000000000668","article-title":"Functional gastrointestinal disorders negatively affect health-related quality of life in MS","volume":"9","author":"Marrie","year":"2019","journal-title":"Neurol. Clin. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1177\/1352458512461393","article-title":"Multiple sclerosis and inflammatory bowel diseases: What we know and what we would need to know!","volume":"19","author":"Alkhawajah","year":"2013","journal-title":"Mult. Scler."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"220","DOI":"10.12968\/bjon.2010.19.4.46783","article-title":"Bowel problems and coping strategies in people with multiple sclerosis","volume":"19","author":"Norton","year":"2010","journal-title":"Br. J. Nurs."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Nouri, M., Bredberg, A., Westr\u00f6m, B., and Lavasani, S. (2014). Intestinal barrier dysfunction develops at the onset of experimental autoimmune encephalomyelitis, and can be induced by adoptive transfer of auto-reactive T cells. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0106335"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"100082","DOI":"10.1016\/j.jtauto.2021.100082","article-title":"Increased intestinal permeability in primary Sj\u00f6gren\u2019s syndrome and multiple sclerosis","volume":"4","author":"Bredberg","year":"2021","journal-title":"J. Transl. Autoimmun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/imr.13162","article-title":"Neutrophil-T cell crosstalk and the control of the host inflammatory response","volume":"314","author":"Bert","year":"2023","journal-title":"Immunol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1182\/blood-2009-04-216085","article-title":"Evidence for a cross-talk between human neutrophils and Th17 cells","volume":"115","author":"Pelletier","year":"2010","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/mi.2012.24","article-title":"The role of neutrophils during intestinal inflammation","volume":"5","author":"Fournier","year":"2012","journal-title":"Mucosal Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"590409","DOI":"10.1155\/2014\/590409","article-title":"Interactions between neutrophils, Th17 Cells, and chemokines during the initiation of experimental model of multiple sclerosis","volume":"2014","author":"Wojkowska","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_10","first-page":"9106","article-title":"Mast cell deficiency exacerbates inflammatory bowel symptoms in interleukin-10-deficient mice","volume":"20","author":"Zhang","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_11","first-page":"534","article-title":"IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis","volume":"118","author":"Sugimoto","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_12","first-page":"2169","article-title":"Role of TH-17 Cells in Rheumatic and Other Autoimmune Diseases","volume":"20","author":"Volin","year":"2011","journal-title":"Rheumatology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/0140-6736(90)93237-J","article-title":"Antimicrobial actions of calcium binding leucocyte L1 protein, calprotectin","volume":"336","author":"Steinbakk","year":"1990","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1097\/00054725-200606000-00013","article-title":"Role of fecal calprotectin as a biomarker of intestinal inflammation in inflammatory bowel disease","volume":"12","author":"Konikoff","year":"2006","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1136\/adc.74.2.136","article-title":"Calprotectin as a marker of inflammation in cystic fibrosis","volume":"74","author":"Golden","year":"1996","journal-title":"Arch. Dis. Child."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1080\/030097402320817077","article-title":"Leukocyte protein calprotectin and outcome in rheumatoid arthritis: A longitudinal study","volume":"31","author":"Madland","year":"2002","journal-title":"Scand. J. Rheumatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/j.0906-6705.2005.00271.x","article-title":"Early activation of cutaneous vessels and epithelial cells is characteristic of acute systemic onset juvenile idiopathic arthritis","volume":"14","author":"Frosch","year":"2005","journal-title":"Exp. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"102520","DOI":"10.1016\/j.msard.2020.102520","article-title":"Biomarkers of inflammation and epithelial barrier function in multiple sclerosis","volume":"46","author":"Olsson","year":"2020","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1016\/S0140-6736(00)03224-4","article-title":"Calprotectin, a faecal marker of organic gastrointestinal abnormality","volume":"356","author":"Fagerhol","year":"2000","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1177\/2050640616650062","article-title":"Does calprotectin level identify a subgroup among patients suffering from irritable bowel syndrome? Results of a prospective study","volume":"5","author":"Melchior","year":"2017","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.jpeds.2008.04.062","article-title":"Increased Gastrointestinal Permeability and Gut Inflammation in Children with Functional Abdominal Pain and Irritable Bowel Syndrome. Journal of Pediatrics","volume":"153","author":"Shulman","year":"2008","journal-title":"J. Pediatr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jneuroim.2009.09.006","article-title":"Calprotectin levels in the cerebrospinal fluid reflect disease activity in multiple sclerosis","volume":"216","author":"Vandvik","year":"2009","journal-title":"J. Neuroimmunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/j.1365-2796.2010.02340.x","article-title":"Faecal calprotectin: A biomarker of gastrointestinal disease in systemic sclerosis","volume":"270","author":"Scheja","year":"2011","journal-title":"J. Intern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.3109\/00365529309098312","article-title":"Faecal calprotectin: A novel test for the diagnosis of colorectal cancer?","volume":"28","author":"Kristinsson","year":"1993","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"435","DOI":"10.3109\/00365521.2011.648953","article-title":"Calprotectin in ankylosing spondylitis\u2014Frequently elevated in feces, but normal in serum","volume":"47","author":"Klingberg","year":"2012","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6782","DOI":"10.3748\/wjg.v18.i46.6782","article-title":"Utility of faecal calprotectin analysis in adult inflammatory bowel disease","volume":"14","author":"Smith","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0304-3940(98)00263-8","article-title":"Serum levels of macrophage-derived protein MRP-8\/14 are elevated in active multiple sclerosis","volume":"247","author":"Bogumil","year":"1998","journal-title":"Neurosci. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.jneuroim.2003.11.005","article-title":"Monocyte activation and disease activity in multiple sclerosis. A longitudinal analysis of serum MRP8\/14 levels","volume":"148","author":"Floris","year":"2004","journal-title":"J. Neuroimmunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1080\/003655200750024551","article-title":"Relationship between Intestinal Permeability and Calprotectin Concentration in Gut Lavage Fluid","volume":"35","author":"Berstad","year":"2000","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13317-021-00149-1","article-title":"Short-chain fatty acids and intestinal inflammation in multiple sclerosis: Modulation of female susceptibility by microbial products?","volume":"12","author":"Becker","year":"2021","journal-title":"Auto Immun. Highlights"},{"key":"ref_31","first-page":"CD006097","article-title":"Natalizumab for induction of remission in Crohn\u2019s disease","volume":"8","author":"Nelson","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1016\/0016-5085(84)90202-6","article-title":"Quantitative Assay for Acute Intestinal Inflammation Based on Myeloperoxidase Activity Assessment of Inflammation in Rat and Hamster Models","volume":"87","author":"Krawisz","year":"1984","journal-title":"Gastroenterology"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Droeser, R.A., Hirt, C., Eppenberger-Castori, S., Zlobec, I., Viehl, C.T., Frey, D.M., Nebiker, C.A., Rosso, R., Zuber, M., and Amicarella, F. (2013). High Myeloperoxidase Positive Cell Infiltration in Colorectal Cancer Is an Independent Favorable Prognostic Factor. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064814"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.abb.2010.04.008","article-title":"Human myeloperoxidase in innate and acquired immunity","volume":"500","author":"Arnhold","year":"2010","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"318","DOI":"10.3181\/00379727-214-44099","article-title":"Intestinal epithelial barrier dysfunction in Crohn\u2019s disease","volume":"214","author":"Ma","year":"1997","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_36","first-page":"928461","article-title":"Role of Th17 Cells in the Pathogenesis of Human IBD","volume":"2014","year":"2014","journal-title":"ISRN Inflamm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"657622","DOI":"10.3389\/fimmu.2021.657622","article-title":"ILC3, a Central Innate Immune Component of the Gut-Brain Axis in Multiple Sclerosis","volume":"12","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1015372","DOI":"10.3389\/fimmu.2022.1015372","article-title":"Fecal Lcn-2 level is a sensitive biological indicator for gut dysbiosis and intestinal inflammation in multiple sclerosis","volume":"21","author":"Yadav","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10753-010-9201-8","article-title":"Impact of interleukin-17 on macrophage phagocytosis of apoptotic neutrophils and particles","volume":"34","author":"Silverpil","year":"2011","journal-title":"Inflammation"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s11894-010-0131-2","article-title":"Intestinal goblet cells and mucins in health and disease: Recent insights and progress","volume":"12","author":"Kim","year":"2010","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"55","DOI":"10.3390\/pathogens2010055","article-title":"Goblet cells and mucins: Role in innate defense in enteric infections","volume":"2","author":"Kim","year":"2013","journal-title":"Pathogens"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.immuni.2008.11.003","article-title":"Innate and Adaptive Interleukin-22 Protects Mice from Inflammatory Bowel Disease","volume":"29","author":"Zenewicz","year":"2008","journal-title":"Immunity"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"656745","DOI":"10.3389\/fmed.2021.656745","article-title":"Innate Lymphoid Cells as Regulators of Epithelial Integrity: Therapeutic Im-plications for Inflammatory Bowel Diseases","volume":"8","author":"Neurath","year":"2021","journal-title":"Front. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1124\/jpet.102.033951","article-title":"Goblet cell hyperplasia, airway function, and leukocyte infiltration after chronic lipopolysaccharide exposure in conscious guinea pigs: Effects of rolipram and dexamethasone","volume":"302","author":"Toward","year":"2002","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Lavasani, S., Dzhambazov, B., Nouri, M., F\u00e5k, F., Buske, S., Molin, G., Thorlacius, H., Alenfall, J., Jeppsson, B., and Westr\u00f6m, B. (2010). A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0009009"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/20\/15367\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:09:49Z","timestamp":1760130589000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/20\/15367"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,19]]},"references-count":45,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["ijms242015367"],"URL":"https:\/\/doi.org\/10.3390\/ijms242015367","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,19]]}}}