Persistent inflammation and hyperresponsiveness following viral rhinosinusitis.

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.

• Authors: James Joseph Klemens, Kenneth Thompson, Alexander Langerman, Robert M Naclerio
• Journal: The Laryngoscope (Laryngoscope) Vol. 116 Issue 7 Pg. 1236-40 (Jul 2006) ISSN: 0023-852X [Print] United States
• PMID: 16826067 (Publication Type: Comparative Study, Journal Article)

Chemical References

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

Topics

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