title: Local and systemic inflammatory and immunologic reactions to cyathostomin larvicidal therapy in horses.
abstract: Encysted cyathostomin larvae are ubiquitous in grazing horses. Arrested development occurs in this population and can lead to an accumulation of encysted larvae. Large numbers of tissue larvae place the horse at risk for developing larval cyathostominosis. This disease complex is caused by mass emergence of these larvae and is characterized by a generalized acute typhlocolitis and manifests itself as a profuse protein-losing watery diarrhea with a reported case-fatality rate of about 50%. Two anthelmintic formulations have a label claim for larvicidal therapy of these encysted stages; moxidectin and a five-day regimen of fenbendazole. There is limited knowledge about inflammatory and immunologic reactions to larvicidal therapy. This study was designed to evaluate blood acute phase reactants as well as gene expression of pro-inflammatory cytokines, both locally in the large intestinal walls and systemically. Further, mucosal tissue samples were evaluated histopathologically as well as analyzed for gene expression of pro- and anti-inflammatory cytokines, cluster of differentiation (CD) cell surface proteins, and select transcription factors. Eighteen juvenile horses with naturally acquired cyathostomin infections were randomly assigned to three treatment groups; one group served as untreated controls (Group 1), one received a five-day regimen of fenbendazole (10mg/kg) (Group 2), and one group received moxidectin (0.4mg/kg) (Group 3). Horses were treated on day 0 and euthanatized on days 18-20. Serum and whole blood samples were collected on days 0, 5, and 18. All horses underwent necropsy with collection of tissue samples from the ventral colon and cecum. Acute phase reactants measured included serum amyloid A, iron and fibrinogen, and the cytokines evaluated included interferon γ, tumor necrosis factor α, transforming growth factor (TGF)-β, and interleukins 1β, 4, 5, 6, and 10. Transcription factors evaluated were FoxP3, GATA3 and tBet, and CD markers included CD163, CD3z, CD4, CD40, and CD8b. Histopathology revealed an inflammatory reaction with higher levels of lymphocytes, T cells, B cells, eosinophils and fibrous tissue in the moxidectin-treated group compared to controls or horses treated with fenbendazole. No apparent systemic reactions were observed. Expression of IL-5 and TGF-β in intestinal tissues was significantly lower in Group 3 compared to Group 1. This study revealed a subtle inflammatory reaction to moxidectin, which is unlikely to cause clinical issues.
authors.affiliation: Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA. Electronic address: martin.nielsen@uky.edu.
authors.forename: M K
authors.initials: MK
authors.lastname: Nielsen
authors.affiliation: Veterinary Diagnostic Laboratory, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Loynachan
authors.affiliation: Department of Large Animal Sciences, University of Copenhagen, Taastrup, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Jacobsen
authors.affiliation: Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Stewart
authors.affiliation: East Tennessee Clinical Research, Inc., Rockwood, TN, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Reinemeyer
authors.affiliation: Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Horohov
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002432:Cecum / Q000187:drug effects / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000473:pathology; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism; D005273:Fenbendazole / Q000009:adverse effects* / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000276:immunology; D006734:Horse Diseases / Q000139:chemically induced* / Q000469:parasitology / Q000517:prevention & control; D006736:Horses; D007249:Inflammation / Q000097:blood / Q000378:metabolism; D007814:Larva / Q000187:drug effects; D018942:Macrolides / Q000009:adverse effects* / Q000627:therapeutic use; D009929:Organ Size; D013319:Strongyle Infections, Equine / Q000188:drug therapy* / Q000469:parasitology; D013320:Strongyloidea / Q000187:drug effects
chemical_list: D000871:Anthelmintics; D015415:Biomarkers; D016207:Cytokines; D018942:Macrolides; D005273:Fenbendazole; C027837:moxidectin
keywords: Cyathostomin; Fenbendazole; Immunology; Inflammation; Larvicidal; Moxidectin