Persistent inflammation and hyperresponsiveness following viral rhinosinusitis

Laryngoscope. 2006 Jul;116(7):1236-40. doi: 10.1097/01.mlg.0000224526.43698.52.

Abstract

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<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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • CD4 Antigens / immunology
  • CD8 Antigens / immunology
  • Disease Models, Animal
  • Flow Cytometry
  • Histamine / pharmacology
  • Hypersensitivity, Immediate / etiology*
  • Hypersensitivity, Immediate / immunology
  • Mice
  • Mice, Inbred C57BL
  • Nasal Mucosa / immunology*
  • Nasal Mucosa / pathology
  • Nasal Mucosa / virology
  • Receptors, Interleukin-2 / immunology
  • Respirovirus Infections / complications*
  • Respirovirus Infections / virology
  • Rhinitis / complications*
  • Rhinitis / virology
  • Sendai virus / isolation & purification
  • Sinusitis / complications*
  • Sinusitis / virology
  • T-Lymphocytes / immunology*

Substances

  • CD4 Antigens
  • CD8 Antigens
  • Receptors, Interleukin-2
  • Histamine