title: Paracetamol reduces influenza-induced immunopathology in a mouse model of infection without compromising virus clearance or the generation of protective immunity.
abstract: BACKGROUND
  Seasonal influenza A infection affects a significant cohort of the global population annually, resulting in considerable morbidity and mortality. Therapeutic strategies are of limited efficacy, and during a pandemic outbreak would only be available to a minority of the global population. Over-the-counter medicines are routinely taken by individuals suffering from influenza, but few studies have been conducted to determine their effectiveness in reducing pulmonary immunopathology or the influence they exert upon the generation of protective immunity.
  
  
  METHODS
  A mouse model of influenza infection was utilised to assess the efficacy of paracetamol (acetaminophen) in reducing influenza-induced pathology and to examine whether paracetamol affects generation of protective immunity.
  
  
  RESULTS
  Administration (intraperitoneal) of paracetamol significantly decreased the infiltration of inflammatory cells into the airway spaces, reduced pulmonary immunopathology associated with acute infection and improved the overall lung function of mice, without adversely affecting the induction of virus-specific adaptive responses. Mice treated with paracetamol exhibited an ability to resist a second infection with heterologous virus comparable with that of untreated mice.
  
  
  CONCLUSIONS
  Our results demonstrate that paracetamol dramatically reduces the morbidity associated with influenza but does not compromise the development of adaptive immune responses. Overall, these data support the utility of paracetamol for reducing the clinical symptoms associated with influenza virus infection.
authors.affiliation: Department of Infection, Immunity & Biochemistry, School of Medicine, Heath Park, Cardiff CF14 4XN, UK. laudersn@cardiff.ac.uk
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Lauder
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Clark
authors.forename: Rhys L
authors.initials: RL
authors.lastname: Evans
authors.forename: James P
authors.initials: JP
authors.lastname: Hindley
authors.forename: Kathryn
authors.initials: K
authors.lastname: Smart
authors.forename: Heather
authors.initials: H
authors.lastname: Leach
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Kidd
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Broadley
authors.forename: Simon A
authors.initials: SA
authors.lastname: Jones
authors.forename: Matt P
authors.initials: MP
authors.lastname: Wise
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Godkin
authors.forename: Valerie
authors.initials: V
authors.lastname: O'Donnell
authors.forename: Awen M
authors.initials: AM
authors.lastname: Gallimore
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology / Q000627:therapeutic use*; D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects; D053118:Influenza A Virus, H1N1 Subtype; D053122:Influenza A Virus, H3N2 Subtype; D008099:Liver / Q000187:drug effects / Q000503:physiopathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D011720:Pyrazoles / Q000627:therapeutic use; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D013449:Sulfonamides / Q000627:therapeutic use; D019562:Viral Load / Q000187:drug effects; D017201:Virus Shedding / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000082:Acetaminophen; D000068579:Celecoxib; D015232:Dinoprostone