IL-13, a Th2 cytokine, mediates allergic inflammation and airway hyperresponsiveness. A polymorphic variant of human IL-13, R130Q, has been shown to display increased activity in vitro compared to wild type IL-13. We studied whether this variant has enhanced functional activity in vivo using a mouse model.

BALB/c mice were given 0.5-5.0 μg of IL-13 or IL-13 R130Q variant intratracheally daily for three days. Seventy-two hours after the last IL-13 treatment, airways hyperresponsiveness was measured by barometric whole body plethysmography in response to methacholine. The airway inflammation was assessed by bronchoalveolar lavage cell counts and lung histology.

At the highest dose, 5.0 μg, both R130 (wild type) and Q130 IL-13 resulted in significant airway hyperresponsiveness and near equivalent sensitivity to methacholine. Strikingly, at the lowest dose, 0.5 μg, Q130 IL-13 induced significant airway hyperresponsiveness. In contrast, 0.5 μg of R130 IL-13 had no effect over baseline. At the intermediate 1.0μg dose, the Q130 variant resulted in enhanced airway hyperresponsiveness as evidenced by increased sensitivity to methacholine compared with that observed in R130 IL-13-treated mice.

Q130 IL-13 variant has enhanced activity in vivo compared with wild type R130 IL-13.