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Increased expression of eotaxin and its receptor is associated with inflammatory bowel disease (<jats:styled-content style=\"fixed-case\">IBD<\/jats:styled-content>). Activation of eosinophils causes the release of cationic proteins that are neurotoxic such as eosinophil\u2010derived neurotoxin (<jats:styled-content style=\"fixed-case\">EDN<\/jats:styled-content>). Damage to enteric neurons alters neurally controlled functions of the gut correlated with intestinal inflammation. We hypothesized that inhibition of the <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>3\u2010eotaxin axis will prevent inflammation\u2010induced functional changes to the gastrointestinal tract.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Hartley guinea pigs were administered with trinitrobenzene sulfonate (<jats:styled-content style=\"fixed-case\">TNBS<\/jats:styled-content>; 30\u00a0mg\/kg in 30% ethanol) intrarectally to induce colitis. A <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>3 receptor antagonist (<jats:styled-content style=\"fixed-case\">SB<\/jats:styled-content> 328437 [<jats:styled-content style=\"fixed-case\">SB<\/jats:styled-content>3]) was injected intraperitoneally 1\u00a0hour postinduction of colitis. Animals were euthanized 7\u00a0days post\u2010treatment and colon tissues were collected for <jats:italic>ex vivo<\/jats:italic> studies. The <jats:styled-content style=\"fixed-case\">EDN<\/jats:styled-content>\u2010positive eosinophils in the colon, indicating eosinophil activation, were quantified by immunohistochemistry. Effects of <jats:styled-content style=\"fixed-case\">SB<\/jats:styled-content>3 treatment on gross morphological damage, enteric neuropathy, and colonic dysmotility were determined by histology, immunohistochemistry, and organ bath experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The number of <jats:styled-content style=\"fixed-case\">EDN<\/jats:styled-content>\u2010positive eosinophils was significantly increased in the lamina propria in close proximity to myenteric ganglia in inflamed colon. The <jats:styled-content style=\"fixed-case\">TNBS<\/jats:styled-content>\u2010induced inflammation caused significant damage to colonic architecture and inhibition of colonic motility. Treatment with <jats:styled-content style=\"fixed-case\">SB<\/jats:styled-content>3 antagonist attenuated inflammation\u2010associated morphological damage in the colon, reduced infiltration of <jats:styled-content style=\"fixed-case\">EDN<\/jats:styled-content>\u2010positive eosinophils and restored colonic motility to levels comparable to control and sham\u2010treated guinea pigs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion &amp; Inferences<\/jats:title><jats:p>This is the first study demonstrating that inhibition of <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>3\u2010eotaxin axis alleviates enteric neuropathy and restores functional changes in the gut associated with <jats:styled-content style=\"fixed-case\">TNBS<\/jats:styled-content>\u2010induced colitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13391","type":"journal-article","created":{"date-parts":[[2018,7,3]],"date-time":"2018-07-03T08:43:15Z","timestamp":1530607395000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Targeting eotaxin\u20101 and <scp>CCR<\/scp>3 receptor alleviates enteric neuropathy and colonic dysfunction in <scp>TNBS<\/scp>\u2010induced colitis in guinea pigs"],"prefix":"10.1111","volume":"30","author":[{"given":"R. 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Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Stavely","sequence":"additional","affiliation":[{"name":"College of Health and Biomedicine Victoria University  Melbourne Vic. Australia"},{"name":"Institute for Health and Sport Victoria University  Melbourne Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Apostolopoulos","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport Victoria University  Melbourne Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. C.","family":"Bornstein","sequence":"additional","affiliation":[{"name":"Department of Physiology Melbourne University  Melbourne Vic. 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