Role of interleukin-12 and Stat-4 in the regulation of airway inflammationand 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 maj ority of children who acquire a RSV infection do not exhibit severe symptom s. Development of a Th1 response has been associated with resolution of sym ptoms in viral infections and may explain mild RSV illness. The current stu dy investigated the cytokine response observed in mild disease in C57BL/6 m ice that had low airway resistance and mucus production with little pulmona ry inflammation. RSV infection in these mice was accompanied by a fourfold increase in interleukin-12 (IL-12). Treatment of RSV-infected mice with ant i-IL-12 resulted in an increase in airway hyperreactivity, mucus production , and airway inflammation (eosinophilia). Since IL-12 activation is depende nt on Stat-4-mediated intracellular signal transduction, similar experiment s were performed in Stat-4 deficient mice and demonstrated similar results to those obtained from anti-IL-12 treated mice. Again, there was an increas e in airway hyperreactivity and mucus production, and goblet cell hypertrop hy. These studies support the importance of IL-12 in the immune response to RSV infection resulting in resolution of disease and protection from inapp ropriate inflammatory responses.