Role of interleukin-12 and stat-4 in the regulation of airway inflammation and hyperreactivity in respiratory syncytial virus infection.
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.
Tekkanat
K K
KK
Department of Pediatrics, University of Michigan Medical School, 1301 Catherine, Ann Arbor, MI 48109-0602, USA.
Maassab
H
H
Berlin
A A
AA
Lincoln
P M
PM
Evanoff
H L
HL
Kaplan
M H
MH
Lukacs
N W
NW
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004804:Eosinophils / Q000502:physiology; D007249:Inflammation / Q000503:physiopathology; D018664:Interleukin-12 / Q000276:immunology / Q000502:physiology*; D018793:Interleukin-13 / Q000096:biosynthesis; D008168:Lung / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D018357:Respiratory Syncytial Virus Infections / Q000503:physiopathology*; D050797:STAT4 Transcription Factor; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D000906:Antibodies; D004268:DNA-Binding Proteins; D018793:Interleukin-13; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D015534:Trans-Activators; D018664:Interleukin-12