Respiratory syncytial virus-induced airway hyperresponsiveness is independent of IL-13 compared with that induced by allergen
Authors
Jung Won Park ; Christian Taube ; Erwin W. Gelfand ; Debra D. Donaldson ; Azzeddine Dakhama ; Nobuaki Miyahara ; Katsuyuki Takeda ; Annette Balhorn ; Anthony Joetham ; Eun Seok Yang
Citation
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol.112(6) : 1078-1087, 2003
BACKGROUND:
IL-13 is a central mediator of allergen-induced airway hyperresponsiveness (AHR), but its role in respiratory syncytial virus (RSV)-induced AHR is not defined. The combination of allergen exposure and RSV infection is known to increase AHR and lung inflammation, but whether IL-13 regulates this increase is similarly not known.
OBJECTIVE:
Our objective was to determine the role of RSV infection and IL-13 on airway responsiveness and lung inflammation on sensitized and challenged mice.
METHODS:
Using a murine model of RSV infection and allergen exposure, we examined the role of IL-13 in the development of AHR and lung inflammation in IL-13 knockout mice, as well as using a potent IL-13 inhibitor (IL-13i). Mice were sensitized and challenged to allergen, and 6 days after the last challenge, they were infected with RSV. IL-13 was inhibited using an IL-13 receptor alpha(2)-human IgG fusion protein. AHR to inhaled methacholine was measured 6 days after infection, as was bronchoalveolar lavage fluid and lung inflammatory and cytokine responses.
RESULTS:
RSV-induced AHR was unaffected by the IL-13i, despite prevention of goblet cell hyperplasia. Similar results were seen in IL-13-deficient mice. In sensitized and challenged mice, RSV infection significantly increased AHR, and after IL-13i treatment, AHR was significantly reduced, but to the levels seen in RSV-infected mice alone.
CONCLUSIONS:
These results indicate that despite some similarities, the mechanisms leading to AHR induced by RSV are different from those that follow allergen sensitization and challenge. Because IL-13 inhibition is effective in preventing the increases in AHR and mucus production in sensitized and challenged mice infected with RSV, IL-13i could play an important role in preventing the consequences of viral infection in patients with allergic asthma.