A mouse model for investigating the molecular pathogenesis of adenovirus pneumonia.
Intranasal inoculation of type 5 adenovirus (Ad5) produced pneumonia in mice even though the virus did not replicate. To induce the pneumonia, however, a large viral infectious dose was required--i.e., 10(10) plaque-forming units. Four strains of inbred mouse were studied (C57BL/6N, C57BL/10ScN, CBA/N, and C3H/N): all showed similar inflammatory responses, although the greatest infiltration occurred in the C57BL/6N mice. The pathological response to Ad5 infection resembled that previously described in cotton rats: it consisted of overlapping early and late phases, and the infiltration contained primarily lymphocytes and monocytes/macrophages with a scattering of polymorphonuclear leukocytes. The prominent early phase and the presence of polymorphonuclear leukocytes suggested that induction of cytokines may play an important role in the pathogenesis of this pneumonia. Assays showed the appearance of tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), and IL-6 in the infected mouse lungs concomitant with the developing early-phase infiltration. Only IL-6 was found in the peripheral blood. IL-6 reached maximum titers 6-24 hr after infection, whereas maximum levels of TNF-alpha and IL-1 were attained 2-3 days after infection. Specific RNAs for each of these cytokines were demonstrated in the infected lungs. To test the hypothesis that a cytotoxic T-cell response was responsible for the second phase, which primarily consisted of a perivascular and peribronchial infiltration of lymphocytes, Ad5 was used to infect C57BL/10ScN Nu/Nu and parent mice. The nude mice showed a normal early-phase response, but essentially no peribronchial and only minimal perivascular infiltrations occurred.
Ginsberg
H S
HS
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Moldawer
L L
LL
Sehgal
P B
PB
Redington
M
M
Kilian
P L
PL
Chanock
R M
RM
Prince
G A
GA
D000257:Adenoviridae Infections / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D000258:Adenovirus Infections, Human / Q000503:physiopathology; D000260:Adenoviruses, Human; D000818:Animals; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007624:KB Cells; D008168:Lung / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D011024:Pneumonia, Viral / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha