Murine cytomegalovirus-induced interstitial pneumonitis

Elizabeth Fitzpatrick, A. M. Kaplan, P. A. Cohen

Research output: Contribution to journalArticle

Abstract

Interstitial pneumonitis (IP), is a common complication of organ transplantation. One cause of infectious IP is cytomegalovirus (CMV) infection. Because of high mortality, it is crucial to develop effective therapies for CMV-IP. The mechanisms of CMV-IP are poorly understood. Clinical and laboratory studies reveal that the disease may be the result of an immunopathogenic response in the lung. Using a murine model of CMV-induced IP, experiments were performed to characterize the immune response in the lung. Balb/c mice were inoculated intranasally with MCMV followed 24h later with a single injection of cyclophosphamide (CP). By day 14 post-infection (pi), mice developed IP characterized by a mononuclear infiltration of the peribronchiolar areas of the lung. MCMV alone displayed little or no lung inflammation. Mice infected with MCMV+CP demonstrated significantly elevated levels of MCMV IE1 immediate early gene mRNA in comparison to mice treated with MCMV alone. Thus, expression of IE1 mRNA appeared to correlate with IP. The inflammatory changes in the lungs of mice with MCMV+CP suggest that inflammatory mediators are being produced in the lungs of these mice. RT-PCR analysis demonstrated increased expression of IFN-gamma, TNF-alpha, and IL-6 by day 8 post-infection in lungs of mice with MCMV+CP compared to mice treated with MCMV alone. CP alone also induced expression of IFN-gamma, TNF-alpha, and IL-6, although to a lesser extent than MCMV+CP. These studies indicate that CP treatment can induce pro-inflammatory cytokines in the lungs and enhance IE1 gene transcription by MCMV. The contribution of pro-inflammatory cytokines to the development of IP remains to be determined.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998
Externally publishedYes

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Muromegalovirus
Cytomegalovirus
Interstitial Lung Diseases
cyclophosphamide
Cyclophosphamide
pneumonia
lungs
mice
Lung
Interleukin-6
interleukin-6
tumor necrosis factor-alpha
Tumor Necrosis Factor-alpha
Genes
cytokines
Cytokines
Transplantation (surgical)
Messenger RNA
organ transplantation
Immediate-Early Genes

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Murine cytomegalovirus-induced interstitial pneumonitis. / Fitzpatrick, Elizabeth; Kaplan, A. M.; Cohen, P. A.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998.

Research output: Contribution to journalArticle

Fitzpatrick, Elizabeth ; Kaplan, A. M. ; Cohen, P. A. / Murine cytomegalovirus-induced interstitial pneumonitis. In: FASEB Journal. 1998 ; Vol. 12, No. 5.
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