title: Excessive cytokine response to rapid proliferation of highly pathogenic avian influenza viruses leads to fatal systemic capillary leakage in chickens.
abstract: Highly pathogenic avian influenza viruses (HPAIVs) cause lethal infection in chickens. Severe cases of HPAIV infections have been also reported in mammals, including humans. In both mammals and birds, the relationship between host cytokine response to the infection with HPAIVs and lethal outcome has not been well understood. In the present study, the highly pathogenic avian influenza viruses A/turkey/Italy/4580/1999 (H7N1) (Ty/Italy) and A/chicken/Netherlands/2586/2003 (H7N7) (Ck/NL) and the low pathogenic avian influenza virus (LPAIV) A/chicken/Ibaraki/1/2005 (H5N2) (Ck/Ibaraki) were intranasally inoculated into chickens. Ty/Italy replicated more extensively than Ck/NL in systemic tissues of the chickens, especially in the brain, and induced excessive mRNA expression of inflammatory and antiviral cytokines (IFN-γ, IL-1β, IL-6, and IFN-α) in proportion to its proliferation. Using in situ hybridization, IL-6 mRNA was detected mainly in microglial nodules in the brain of the chickens infected with Ty/Italy. Capillary leakage assessed by Evans blue staining was observed in multiple organs, especially in the brains of the chickens infected with Ty/Italy, and was not observed in those infected with Ck/NL. In contrast, LPAIV caused only local infection in the chickens, with neither apparent cytokine expression nor capillary leakage in any tissue of the chickens. The present results indicate that an excessive cytokine response is induced by rapid and extensive proliferation of HPAIV and causes fatal multiple organ failure in chickens.
authors.affiliation: Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan .
authors.forename: Saya
authors.initials: S
authors.lastname: Kuribayashi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakoda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawasaki
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Tanaka
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Okamatsu
authors.forename: Norikazu
authors.initials: N
authors.lastname: Isoda
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Tsuda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sunden
authors.forename: Takashi
authors.initials: T
authors.lastname: Umemura
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakajima
authors.forename: Hideki
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kida
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002199:Capillary Permeability; D002645:Chickens; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D005070:Evans Blue / Q000378:metabolism; D053125:Influenza A Virus, H5N2 Subtype; D057916:Influenza A Virus, H7N1 Subtype; D053126:Influenza A Virus, H7N7 Subtype; D009980:Influenza A virus / Q000502:physiology*; D005585:Influenza in Birds / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D014779:Virus Replication
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; D005070:Evans Blue