( d limit on signal transmission. Or...)Greasing interferon's gears may pave way to greater therapeutic benefits, fewer side effects

"Ordinarily, the interferon signaling system's rate may be slowed because this helper protein interacts with Stat1 at less than the maximum amount," Holtzman says. "It's possible that the maximal setting would be harmful in the long term, because too much interferon could lead to inflammatory diseases. But we may find advantages to increasing Stat1 action in the short term using drug treatments."

Such therapies could allow physicians to turn up the effect of interferon temporarily to treat infections or other disorders and then to turn it back down to normal levels when the patient is cured.

"The potential for this 'rheo-Stat' strategy is exciting," Holtzman says. "As an example, one could improve Stat1 efficiency during the winter months in patients at risk of developing serious viral infections, including children with asthma, heart disease or compromised immune systems."

It may be possible, as well, to screen patients for levels of Stat1 responsiveness and use the same treatment strategy to correct low levels of response, according to Holtzman. The researchers are currently screening newborn infants for levels of Stat1 action and tracking their susceptibility to viral infection.

In addition, the group is studying transgenic mice engineered to carry the same Stat1 mutations that were examined in cells. In this way, the researchers can investigate the benefits of hyper-responsive Stat1 for infection control and cancer treatment in a living organism. These studies lay the foundation for the development of human treatments that use drugs that increase Stat1 responsiveness and consequently enhance the benefits of interferon produced naturally in the body or given as treatment.