Role of interleukin-12 and Stat-4 in the regulation of airway inflammation and hyperreactivity in respiratory syncytial virus infection

K. K. Tekkanat, H. Maassab, A. A. Berlin, P. M. Lincoln, H. L. Evanoff, Mark Kaplan, N. W. Lukacs

Research output: Contribution to journalArticle

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Abstract

Respiratory syncytial virus (RSV) is a respiratory pathogen that can cause significant morbidity in infants and young children. Interestingly, the majority of children who acquire a RSV infection do not exhibit severe symptoms. Development of a Th1 response has been associated with resolution of symptoms in viral infections and may explain mild RSV illness. The current study investigated the cytokine response observed in mild disease in C57BL/6 mice that had low airway resistance and mucus production with little pulmonary inflammation. RSV infection in these mice was accompanied by a fourfold increase in interleukin-12 (IL-12). Treatment of RSV-infected mice with anti-IL-12 resulted in an increase in airway hyperreactivity, mucus production, and airway inflammation (eosinophilia). Since IL-12 activation is dependent on Stat-4-mediated intracellular signal transduction, similar experiments were performed in Stat-4 deficient mice and demonstrated similar results to those obtained from anti-IL-12 treated mice. Again, there was an increase in airway hyperreactivity and mucus production, and goblet cell hypertrophy. These studies support the importance of IL-12 in the immune response to RSV infection resulting in resolution of disease and protection from inappropriate inflammatory responses.

Original languageEnglish (US)
Pages (from-to)631-638
Number of pages8
JournalAmerican Journal of Pathology
Volume159
Issue number2
StatePublished - 2001

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Respiratory Syncytial Virus Infections
Interleukin-12
Respiratory Syncytial Viruses
Inflammation
Mucus
Airway Resistance
Goblet Cells
Eosinophilia
Virus Diseases
Inbred C57BL Mouse
Hypertrophy
Signal Transduction
Pneumonia
Cytokines
Morbidity

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Tekkanat, K. K., Maassab, H., Berlin, A. A., Lincoln, P. M., Evanoff, H. L., Kaplan, M., & Lukacs, N. W. (2001). Role of interleukin-12 and Stat-4 in the regulation of airway inflammation and hyperreactivity in respiratory syncytial virus infection. American Journal of Pathology, 159(2), 631-638.

Role of interleukin-12 and Stat-4 in the regulation of airway inflammation and hyperreactivity in respiratory syncytial virus infection. / Tekkanat, K. K.; Maassab, H.; Berlin, A. A.; Lincoln, P. M.; Evanoff, H. L.; Kaplan, Mark; Lukacs, N. W.

In: American Journal of Pathology, Vol. 159, No. 2, 2001, p. 631-638.

Research output: Contribution to journalArticle

Tekkanat, KK, Maassab, H, Berlin, AA, Lincoln, PM, Evanoff, HL, Kaplan, M & Lukacs, NW 2001, 'Role of interleukin-12 and Stat-4 in the regulation of airway inflammation and hyperreactivity in respiratory syncytial virus infection', American Journal of Pathology, vol. 159, no. 2, pp. 631-638.
Tekkanat, K. K. ; Maassab, H. ; Berlin, A. A. ; Lincoln, P. M. ; Evanoff, H. L. ; Kaplan, Mark ; Lukacs, N. W. / Role of interleukin-12 and Stat-4 in the regulation of airway inflammation and hyperreactivity in respiratory syncytial virus infection. In: American Journal of Pathology. 2001 ; Vol. 159, No. 2. pp. 631-638.
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