Purpose of the Study. Interleukin-10 (IL-10) has been shown to inhibit allergen-induced airway hyperresponsiveness and inflammation. This study evaluates whether IL-19, a member of the IL-10 family, is associated with asthma.
Study Population. The authors investigated IL-19 levels in 100 asthmatic patients, aged 3 to 12 years, as well as 50 healthy adults and 50 age-matched children. A dust mite–induced mouse model of asthma was also used to study the association of IL-19 with asthma.
Methods. Cytokine levels were quantified by enzyme-linked immunosorbent assay. IL-19 levels were measured in all study subjects, but among asthmatic patients, the levels of IL-4 and IL-13 were analyzed in the 27 patients with the highest and 25 patients with the lowest IL-19 levels. By using a dust mite–sensitized murine asthma model, IL-19 levels were measured in asthmatic and control mice. To test whether IL-19 upregulates T-helper 2 (Th2) cytokines, IL-19 complementary DNA was injected into healthy mice using intramuscular electroporation, and serum levels of IL-4, IL-5, IL-10, and IL-13 were later monitored. After injection of IL-19 into asthmatic mice, IL-13 and immunoglobulin E (IgE) levels were measured. To determine if IL-19 could induce Th2 cytokine production in vitro, IL-19 was incubated with CD4+ T cells and IL-4, IL-5, IL-10, and IL-13 levels were quantified in the cell-culture supernatant.
Results. Among asthmatic patients, the serum level of IL-19 was twice that of healthy controls, and those with a high level of IL-19 also had high levels of IL-4 and IL-13. In the murine asthma model, asthmatic mice also had IL-19 levels twice that of healthy control mice. Injection of the IL-19 gene into healthy mice induced production of IL-4, IL-5, and IL-10 but not IL-13. IL-19 upregulated IL-13 in asthmatic mice and also upregulated IgE production. In vitro, IL-19 was associated with increased IL-4, IL-5, IL-10, and IL-13 production by activated cells.
Conclusions. IL-19 upregulates production of Th2 cytokines in activated T cells and may be an important molecule in the pathogenesis of asthma.
Reviewer Comments. The Th2 cytokines upregulated by IL-19 play crucial roles in the pathogenesis of asthma. IL-13 regulates airway hypersensitivity and mucus hypersecretion; IL-4 is critical for IgE antibody switching; and IL-5 plays a key role in eosinophil maturation. The findings from this study suggest that IL-19 is another potentially important molecule in asthma pathogenesis and may be responsible, at least in part, for upregulation of Th2 cytokines that are critical to the development of allergic disease.
- Copyright © 2006 by the American Academy of Pediatrics