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. CONCLUSION: 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.