An asthma attack is nothing to sneeze at. In a dramatic--and dangerous--overreaction by the immune system, the lungs pump out mucus and inflammatory molecules, clogging and swelling constricted airways. In tomorrow's Science, two independent teams present evidence that an immune system messenger called interleukin-13 (IL-13) may be a key culprit in such attacks. The results come from mouse studies, but if they hold up in humans, they suggest two promising targets for antiasthma therapies.
Although IL-13 was known to play a role in asthma, until now it was difficult to distinguish its contribution from that of its sibling molecule, interleukin-4. But a new molecule that selectively mops up IL-13 from airways has allowed the two teams of scientists to clarify the mischief of these twin messengers--and suggests that IL-13 deserves a greater share of blame in attacks.
The new molecule binds to IL-13, preventing it from attaching to its receptors on immune system cells. In independent work, teams led by immunologist Marsha Wills-Karp of Johns Hopkins University and David Corry of the University of California, San Francisco, both found that the IL-13 blocker lessened the signs of asthma in mice. In addition, Corry's team tested IL-13 and IL-4 themselves by applying a drop of one or the other directly in the mice's nasal passages. The mice that received IL-13 appeared to develop worse asthma symptoms. "While IL-4 plays a role," Corry says, "IL-13 may be more potent."
A promising drug target, say several scientists, is the portion of the receptor molecule on immune system cells that is shared by both IL-4 and IL-13. Several companies are already seeking an effective way to block the receptor's signaling. The interleukin molecules "won't give you asthma without that receptor," Corry says. "That kind of bottleneck is the perfect target for designing new therapies."