A kinetic study of immune mediators in the lungs of mice infected with influenza A virus.
We investigated a broad spectrum of immunoactive mediators in a mouse model of influenza. ICR mice (4-5 wk old) that were infected with a 10 LD50 dose of influenza A/PR8/34 virus died after 6 days without evidence of bacterial superinfection. Maximal virus titers were reached by day 2 postinfection, whereas the multifocal pneumonia with mononuclear cell infiltration reached its maximum at the end of infection. We measured the cytokines IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-6, IFN-gamma, TNF-alpha, granulocyte (G)/macrophage (M)-CSF, G-CSF, M-CSF, and the lipid mediators leukotriene B4 and platelet-activating factor in the cellfree bronchoalveolar lavage fluid of mice during infection. We found an early increase of IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, GM-CSF, IFN-gamma, and leukotriene B4. Levels of these factors peaked between 36 h and day 3 postinfection, with the exception of IL-6 that remained at elevated levels throughout infection. G-CSF and M-CSF increased slowly and reached a maximum by day 5 postinfection. We were unable to detect IL-2, IL-3, or IL-4. PAF remained at the same level throughout infection. Our results suggest that lung-resident cells, and possibly the alveolar macrophages, participate actively in the onset of the inflammatory response against the invading virus. The inability to detect the T cell products IL-2, IL-3, and IL-4 was unexpected considering the role of T cells in the elimination of the virus in infected mice. Our observation confirms thus earlier findings about the inability of specific T cell clones to elicit an unspecific antiviral effect.
Hennet
T
T
Institute of Veterinary Virology, University of Berne, Switzerland.
Ziltener
H J
HJ
Frei
K
K
Peterhans
E
E
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D009980:Influenza A virus / Q000276:immunology; D007975:Leukotriene B4 / Q000378:metabolism; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology; D010972:Platelet Activating Factor / Q000378:metabolism; D013997:Time Factors
D016207:Cytokines; D010972:Platelet Activating Factor; D007975:Leukotriene B4