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Persistent Inflammation and Hyperresponsiveness Following Viral Rhinosinusitis
Author(s) -
Klemens James Joseph,
Thompson Kenneth,
Langerman Alexander,
Naclerio Robert M.
Publication year - 2006
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1097/01.mlg.0000224526.43698.52
Subject(s) - flow cytometry , immunology , cd8 , sinusitis , sendai virus , inflammation , histamine , virus , cd3 , otitis , medicine , biology , virology , antigen , surgery
Objectives: To develop a murine model of viral rhinosinusitis. Study Design: 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 ≤ .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 ≤ .03) and neutrophils ( P ≤ .02) compared with controls. This inflammation resolved by day 10. On day 38, mice inoculated with SeV had significantly more CD8+ ( P ≤ .044) and CD4+CD25+ ( P ≤ .017) cells than did controls. On day 8, there was a significant increase in both sneezing ( P ≤ .002) and nasal rubbing ( P ≤ .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.