title: Interleukin-6 is increased in plasma and cerebrospinal fluid of community-dwelling domestic dogs with acute ischaemic stroke.
abstract: Inflammatory cytokines are potential modulators of infarct progression in acute ischaemic stroke, and are therefore possible targets for future treatment strategies. Cytokine studies in animal models of surgically induced stroke may, however, be influenced by the fact that the surgical intervention itself contributes towards the cytokine response. Community-dwelling domestic dogs suffer from spontaneous ischaemic stroke, and therefore, offer the opportunity to study the cytokine response in a noninvasive set-up. The aims of this study were to investigate cytokine concentrations in plasma and cerebrospinal fluid (CSF) in dogs with acute ischaemic stroke and to search for correlations between infarct volume and cytokine concentrations. Blood and CSF were collected from dogs less than 72 h after a spontaneous ischaemic stroke. Infarct volumes were estimated on MRIs. Interleukin (IL)-2, IL-6, IL-8, IL-10 and tumour necrosis factor in the plasma, CSF and brain homogenates were measured using a canine-specific multiplex immunoassay. IL-6 was significantly increased in plasma (P=0.04) and CSF (P=0.04) in stroke dogs compared with healthy controls. The concentrations of other cytokines, such as tumour necrosis factor and IL-2, were unchanged. Plasma IL-8 levels correlated significantly with infarct volume (Spearman's r=0.8, P=0.013). The findings showed increased concentrations of IL-6 in the plasma and CSF of dogs with acute ischaemic stroke comparable to humans. We believe that dogs with spontaneous stroke offer a unique, noninvasive means of studying the inflammatory processes that accompany stroke while reducing confounds that are unavoidable in experimental models.
authors.affiliation: aDepartment of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg bCentre of Functionally Integrative Neuroscience, Aarhus University, Aarhus cDepartment of Neurobiology Research, Institute of Molecular Medicine dBRIDGE (Brain Research - Inter-Disciplinary Guided Excellence), Department of Clinical Research, University of Southern Denmark eDepartment of Neurology, Odense University Hospital, Odense, Denmark fExperimental Neuroinflammation Laboratory, Department of Experimental Medical Science, BMC, Lund University, Lund, Sweden gDavies Veterinary Specialists, Hitchin hFitzpatrick Referrals, Surrey iDepartment of Pharmacology, University of Oxford, Oxford, UK *Shared senior authorship.
authors.forename: Hanne
authors.initials: H
authors.lastname: Gredal
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Thomsen
authors.forename: Antonio
authors.initials: A
authors.lastname: Boza-Serrano
authors.forename: Laurent
authors.initials: L
authors.lastname: Garosi
authors.forename: Clare
authors.initials: C
authors.lastname: Rusbridge
authors.forename: Daniel
authors.initials: D
authors.lastname: Anthony
authors.forename: Arne
authors.initials: A
authors.lastname: Møller
authors.forename: Bente
authors.initials: B
authors.lastname: Finsen
authors.forename: Tomas
authors.initials: T
authors.lastname: Deierborg
authors.forename: Kate L
authors.initials: KL
authors.lastname: Lambertsen
authors.forename: Mette
authors.initials: M
authors.lastname: Berendt
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000000981:diagnostic imaging / Q000209:etiology; D002545:Brain Ischemia / Q000150:complications; D016207:Cytokines / Q000097:blood / Q000134:cerebrospinal fluid; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D015850:Interleukin-6 / Q000097:blood* / Q000134:cerebrospinal fluid*; D008279:Magnetic Resonance Imaging; D008297:Male; D013223:Statistics as Topic; D020521:Stroke / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000209:etiology
chemical_list: D016207:Cytokines; D015850:Interleukin-6