Persistent inflammation and hyperresponsiveness following viral rhinosinusitis.
OBJECTIVE
To develop a murine model of viral rhinosinusitis.


METHODS
Randomized, controlled, animal model.


METHODS
Mice were intranasally inoculated with Sendai virus (SeV) or ultraviolet (UV)-inactivated virus. On days 3 and 10 postinfection, nasal lavage fluid was obtained for viral culture. On days 4, 10, and 38 postinfection, sinus mucosa was harvested and analyzed by flow cytometry for CD3-, CD4-, CD8-, CD25-, CD11b-, CCR3-, and GR1-positive cells. Nasal hyperresponsiveness to histamine challenge was measured on days 8 and 36 postinoculation.


RESULTS
On day 3, viral cultures were positive from all SeV-inoculated mice but from none of the UV-inactivated mice (P<or=.0039). There was no growth of virus from either group on day 10. On day 4, flow cytometry on SeV-infected sinus cells showed a significant increase in macrophages (P<or=.03) and neutrophils (P<or=.02) compared with controls. This inflammation resolved by day 10. On day 38, mice inoculated with SeV had significantly more CD8+ (P<or=.044) and CD4+CD25+ (P<or=.017) cells than did controls. On day 8, there was a significant increase in both sneezing (P<or=.002) and nasal rubbing (P<or=.002) in the SeV-infected group to histamine challenge compared with controls. This difference continued to day 36.


CONCLUSIONS
Inoculation with SeV results in an acute infection that resolves spontaneously within 10 days. Infected mice develop a significant increase in T-suppressor and T-regulatory cells after resolution of the acute infection, which persists for at least 38 days. The persistence of these T cells is associated with hyperresponsiveness to histamine. This mouse model has some parallels to chronic rhinosinusitis after a viral infection in humans and should allow us to clarify the pathophysiology of this disease.
Klemens
James Joseph
JJ
Department of Surgery, Section of Otolaryngology-Head and Neck Surgery, University of Chicago, Chicago, IL 60637-1035, USA.
Thompson
Kenneth
K
Langerman
Alexander
A
Naclerio
Robert M
RM
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006632:Histamine / Q000494:pharmacology; D006969:Hypersensitivity, Immediate / Q000209:etiology* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009297:Nasal Mucosa / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D010253:Respirovirus Infections / Q000150:complications* / Q000821:virology; D012220:Rhinitis / Q000150:complications* / Q000821:virology; D029082:Sendai virus / Q000302:isolation & purification; D012852:Sinusitis / Q000150:complications* / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D015375:Receptors, Interleukin-2; D006632:Histamine