title: Rapamycin Does Not Impede Survival or Induction of Antibody Responses to Primary and Heterosubtypic Influenza Infections in Mice.
abstract: Impairment of immune defenses can contribute to severe influenza infections. Rapamycin is an immunosuppressive drug often used to prevent transplant rejection and is currently undergoing clinical trials for treating cancers and autoimmune diseases. We investigated whether rapamycin has deleterious effects during lethal influenza viral infections. We treated mice with two concentrations of rapamycin and infected them with A/Puerto Rico/8/1934 (A/PR8), followed by a heterosubtypic A/Hong Kong/1/68 (A/HK68) challenge. Our data show similar morbidity, mortality, and lung viral titer with both rapamycin treatment doses compared to untreated controls, with a delay in morbidity onset in rapamycin high dose recipients during primary infection. Rapamycin treatment at high dose also led to increase in percent cytokine producing T cells in the spleen. However, all infected animals had similar serum antibody responses against A/PR8. Post-A/HK68 challenge, rapamycin had no impeding effect on morbidity or mortality and had similar serum antibody levels against A/PR8 and A/HK68. We conclude that rapamycin treatment does not adversely affect morbidity, mortality, or antibody production during lethal influenza infections.
authors.affiliation: 1 Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia .
authors.forename: Justine S
authors.initials: JS
authors.lastname: Liepkalns
authors.affiliation: 1 Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia .
authors.forename: Aseem
authors.initials: A
authors.lastname: Pandey
authors.affiliation: 1 Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia .|2 Pathology and Laboratory Medicine, Emory University , Atlanta, Georgia .
authors.forename: Amelia R
authors.initials: AR
authors.lastname: Hofstetter
authors.affiliation: 1 Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia .
authors.forename: Amrita
authors.initials: A
authors.lastname: Kumar
authors.affiliation: 1 Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia .
authors.forename: Enitra N
authors.initials: EN
authors.lastname: Jones
authors.affiliation: 1 Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia .
authors.forename: Weiping
authors.initials: W
authors.lastname: Cao
authors.affiliation: 1 Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia .
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: 1 Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia .
authors.forename: Min Z
authors.initials: MZ
authors.lastname: Levine
authors.affiliation: 1 Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia .
authors.forename: Suryaprakash
authors.initials: S
authors.lastname: Sambhara
authors.affiliation: 1 Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia .
authors.forename: Shivaprakash
authors.initials: S
authors.lastname: Gangappa
mesh_terms: D000818:Animals; D000917:Antibody Formation; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D009980:Influenza A virus / Q000276:immunology*; D008168:Lung / Q000821:virology; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000821:virology; D020123:Sirolimus / Q000008:administration & dosage*; D013154:Spleen / Q000276:immunology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D019562:Viral Load
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D020123:Sirolimus