title: Slow release cortisol implants result in impaired innate immune responses and higher infection prevalence following experimental challenge with infectious pancreatic necrosis virus in Atlantic salmon (Salmo salar) parr.
abstract: Stress can affect the immune system and increase susceptibility to various diseases but knowledge of the underlying mechanisms is scarce. There is a complex interaction between the immune system and the endocrine system of vertebrates. In fish, cortisol is a key hormone regulating stress response and recent studies have also suggested that this hormone can affect the immune system, where cortisol is mainly regarded as an immunosuppressive factor. The aim of the present study was to examine the impact of chronically elevated levels of cortisol on the immune response and susceptibility to experimental infection with infectious pancreatic necrosis virus (IPNV). Further, the effect of IPNV challenge on circulating levels of cortisol was investigated. Atlantic salmon parr were implanted intraperitoneally with sustained-release implants of bovine of cortisol (50 μg cortisol g(-1) body weight in an implant based on vegetable lipids). Vehicle implants were used as control (sham-injected). At 45 days after implantation (DAI), fish were challenged with a low virulent isolate of IPNV (by immersion). Samples of plasma, liver and head kidney was taken from fish before and 24 h, 48 h, 7 days week and 21 days post infection (DPI). Cortisol level in plasma was measured using radioimmunoassay and gene expression in liver and head kidney was analyzed with real-time PCR (RT-PCR). Infection prevalence in infected fish was assessed by virus culture and RT-PCR of head kidney samples. Cortisol implantation compared with sham-implanted fish had increased levels of plasma cortisol at 45 DAI. The relative expression of Interferon alpha-1 (IFNα-1), Myxo virus-1 Mx, Heat-shock protein 70 (HSP70), Serum amyloid A (SAA), Glucocorticoid receptor (GR) and Heat-shock protein 90 (HSP90) tends to be down-regulated by cortisol implantation. There was a higher prevalence of fish with detectable levels of IPNV, as measured by cell culture and RT-PCR, in the cortisol-implanted group challenged with IPNV (0 = 0.0305) relative to the group that received a sham implantation. Further, cortisol seems to delay the induction of the antiviral IFNα-1 pathway and Mx mRNA expression. This study shows that elevated plasma cortisol level leads to an impaired innate immune response, and higher virus (IPNV) prevalence in Atlantic salmon parr.
authors.affiliation: Norwegian School of Veterinary Science, Department of Basic Sciences and Aquatic Medicine, Oslo, Norway.
authors.forename: K
authors.initials: K
authors.lastname: Gadan
authors.forename: I Singh
authors.initials: IS
authors.lastname: Marjara
authors.forename: H
authors.initials: H
authors.lastname: Sundh
authors.forename: K
authors.initials: K
authors.lastname: Sundell
authors.forename: Ø
authors.initials: Ø
authors.lastname: Evensen
mesh_terms: D000818:Animals; D018175:Birnaviridae Infections / Q000276:immunology / Q000662:veterinary*; D005393:Fish Diseases / Q000276:immunology*; D005786:Gene Expression Regulation; D006854:Hydrocortisone / Q000097:blood*; D007113:Immunity, Innate; D018061:Infectious pancreatic necrosis virus / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D020317:Salmo salar; D013312:Stress, Physiological
chemical_list: D006854:Hydrocortisone