title: Kinetics of pro-inflammatory cytokines, interleukin-10, and virus neutralising antibodies during acute ephemeral fever virus infections in Brahman cattle.
abstract: While fever and inflammation are hallmark features of bovine ephemeral fever (BEF), the cytokine networks that underlie the acute phase of the disease have not been empirically defined in cattle. This study characterised the plasma kinetics of proinflammatory cytokines (IL-1β, IL-6, TNF-α) and IL-10 during acute BEF and elucidated on the relationship between the onset of the virus neutralizing antibody response and resolution of viraemia in natural BEF virus (BEFV) infections in cattle. Plasma from three BEFV-infected and three uninfected cattle was tested for the study cytokines by a cELISA, viraemia monitored by qRT-PCR, and virus neutralizing antibody titres determined using a standard protocol. Unlike the negative controls, plasma concentrations of IL-1β, TNF-α, IL-6, and IL-10 were consistently increased in the three virus-infected animals. Two of the infected heifers were recumbent and pyrexic on the first day of monitoring and increased cytokine production was already in progress by the time viraemia was detected in all the three infected animals. In all the virus-infected heifers, IL-1β was the most strongly expressed cytokine, IL-6 and IL-10 manifested intermediate plasma concentrations while TNF-α was the least expressed and demonstrated bi-phasic peaks three and five days after the onset of pyrexia. In two of the BEFV-infected heifers, viraemia resolved on the day of seroconversion while in the other infected animal, viral RNA was detectable up to three days after seroconversion. The present data document variable increase in plasma IL-1β, IL-6, TNF-α, and IL-10 during natural BEFV infections and the fact that upregulation of all but TNF-α precedes seroconversion. In addition to virus neutralising antibodies, it is likely that cytokine-mediated cellular mechanisms may be required for resolution of viraemia in BEF. Considering the anti-inflammatory properties of IL-10, its upregulation may potentially antagonise the fever response in BEFV-infected cattle.
authors.affiliation: Berrimah Veterinary Laboratories, Department of Primary Industry & Fisheries, GPO Box 3000, Darwin, NT 0801, Australia. Electronic address: Robert.Barigye@nt.gov.au.
authors.forename: R
authors.initials: R
authors.lastname: Barigye
authors.affiliation: Berrimah Veterinary Laboratories, Department of Primary Industry & Fisheries, GPO Box 3000, Darwin, NT 0801, Australia.
authors.forename: L F
authors.initials: LF
authors.lastname: Melville
authors.affiliation: Berrimah Veterinary Laboratories, Department of Primary Industry & Fisheries, GPO Box 3000, Darwin, NT 0801, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Davis
authors.affiliation: Berrimah Veterinary Laboratories, Department of Primary Industry & Fisheries, GPO Box 3000, Darwin, NT 0801, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Walsh
authors.affiliation: Berrimah Veterinary Laboratories, Department of Primary Industry & Fisheries, GPO Box 3000, Darwin, NT 0801, Australia.
authors.forename: N
authors.initials: N
authors.lastname: Hunt
authors.affiliation: Berrimah Veterinary Laboratories, Department of Primary Industry & Fisheries, GPO Box 3000, Darwin, NT 0801, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Hunt
authors.affiliation: Berrimah Veterinary Laboratories, Department of Primary Industry & Fisheries, GPO Box 3000, Darwin, NT 0801, Australia.
authors.forename: N
authors.initials: N
authors.lastname: Elliot
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral / Q000097:blood*; D002417:Cattle; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004810:Ephemeral Fever / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D018115:Ephemeral Fever Virus, Bovine; D005260:Female; D005334:Fever / Q000662:veterinary; D000069078:Seroconversion; D013997:Time Factors; D014766:Viremia
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016207:Cytokines
keywords: Bovine ephemeral fever; Cytokines; Fever; Humoral immunity; Innate immunity