title: Hematological parameters in the early phase of influenza A virus infection in differentially susceptible inbred mouse strains.
abstract: BACKGROUND
  Hematological parameters have not received much attention in small animal models of infection, particularly at very early time points. We therefore studied changes in leukocyte and thrombocyte numbers in a mouse model of influenza A virus (IAV) infection, including measurements within the first 24 h after infection, and also assessing effects, if any, of the infection/anesthesia procedure on these parameters.
  
  
  METHODS
  DBA/2J and C57BL/6J mice (n = 5-8 per observation) were evaluated in a time course experiment of IAV infection, focusing on early time points. After anesthesia with ketamine/xylazine, a suspension of 2 × 10(3) focus forming units of the mouse-adapted IAV strain A/Puerto Rico/8/1934 (H1N1) in 20 µl sterile PBS, or 20 µl sterile PBS only ("mock treatment"), were instilled intranasally. Weight loss was assessed daily, and eight common hematological parameters and viral hemagglutinin (HA) mRNA expression were determined after 6, 12, 18, 24, 48 and 120 h.
  
  
  RESULTS
  Hematological differences between the strains were apparent even in untreated mice. Infection-dependent changes, in particular increased granulocyte and decreased lymphocyte counts, were first detectable after 18 h in DBA/2J, were fully manifest in both strains at 48 h, and were usually more pronounced in the DBA/2J mice. In this strain, relative granulocyte and lymphocyte counts and the granulocyte/lymphocyte ratio correlated with viral HA mRNA expression and weight loss. In C57BL/6J, hematological parameters did not correlate with weight loss, but HA mRNA expression correlated weakly with total leukocyte counts, granulocyte/lymphocyte ratio, relative and absolute granulocyte counts, and relative lymphocyte counts. Significant changes due to mock treatment were mild and were detected only in C57BL/6J.
  
  
  CONCLUSIONS
  This study underscores the value of hematological parameters in monitoring disease evolution in the early phase of IAV infection, and likely other pathogens. The hematological response to infection may differ significantly among inbred mouse strains.
authors.affiliation: Institute for Experimental Infection Research, TWINCORE Centre for Experimental and Clinical Infection Research, Feodor-Lynen-Str. 7, 30625, Hannover, Germany. Matthias.Preusse@helmholtz-hzi.de.|Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124, Brunswick, Germany. Matthias.Preusse@helmholtz-hzi.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusse
authors.affiliation: Bioinformatics, Helmholtz Centre for Infection Research, Brunswick, Germany. Klaus.Schughart@helmholtz-hzi.de.|University of Veterinary Medicine, Hannover, Germany. Klaus.Schughart@helmholtz-hzi.de.|University of Tennessee Health Science Center, Memphis, TN, USA. Klaus.Schughart@helmholtz-hzi.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Schughart
authors.affiliation: Department of Infection Genetics, Helmholtz Centre for Infection Research, Brunswick, Germany. Esther.Wilk@helmholtz-hzi.de.
authors.forename: Esther
authors.initials: E
authors.lastname: Wilk
authors.affiliation: Bioinformatics, Helmholtz Centre for Infection Research, Brunswick, Germany. Frank.Klawonn@helmholtz-hzi.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Klawonn
authors.affiliation: Institute for Experimental Infection Research, TWINCORE Centre for Experimental and Clinical Infection Research, Feodor-Lynen-Str. 7, 30625, Hannover, Germany. Frank.Pessler@twincore.de.|Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124, Brunswick, Germany. Frank.Pessler@twincore.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Pessler
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000821:virology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D054884:Host-Pathogen Interactions; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000472:pathogenicity*; D007958:Leukocyte Count; D007962:Leukocytes / Q000821:virology; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009976:Orthomyxoviridae Infections / Q000097:blood* / Q000821:virology; D010976:Platelet Count; D012333:RNA, Messenger / Q000097:blood; D012367:RNA, Viral / Q000097:blood; D013045:Species Specificity; D013997:Time Factors; D015431:Weight Loss
chemical_list: D015415:Biomarkers; C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D012333:RNA, Messenger; D012367:RNA, Viral