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Gamma interferon slays microbial invaders.

Gamma Interferon Slays Microbial Invaders

A recently approved drug that stimulates the immune system helps fight off life-threatening infections in people with a rare, inherited disorder called chronic granulomatous disease (CGD), an international study reveals. Elated researchers suggest that the genetically engineered drug, called gamma interferon, may one day benefit a broad range of patients with damaged or immature immune systems, including premature infants, cancer victims and the elderly.

"This is a dramatic result for patients who have CGD," says hematologist R. Alan Ezekowitz of Harvard Medical School, a principal researcher on the study.

"It certainly sets the tone for launching investigations into other settings," adds coauthor John I. Gallin of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

Researchers launched the multicenter trial in 1988 after demonstrating that gamma interferon appeared to compensate for the immune system defect that causes CGD (SN: 7/23/88, p.53). The disorder affects immune cells called phagocytes, reducing their ability to release microbe-killing substances known as superoxide anions. The phagocytes can still engulf microbial invaders, but they can't deliver a powerful knockout punch -- a flaw that leaves patients vulnerable to repeated bouts of bacterial and fungal infection. The disorder also causes a chronic inflammatory response in which tumor-like masses, or granulomas, block the stomach, intestines and other organs. Although preventive antibiotic therapy has improved the outlook for people with CGD, many still die in childhood or as young adults.

U.S., Swedish, Danish and Swiss researchers studied the effects of gamma interferon in a group of 128 children and young adults with the inherited disease. In the Feb. 21 NEW ENGLAND JOURNAL OF MEDICINE, they report that the drug, compared with placebo, reduced the frequency of serious infection by about 70 percent -- a track record that promises to extend patients' life expectancy.

The investigators randomly assigned individuals to receive injections of placebo or gamma interferon three times weekly for up to one year. In addition, all participants continued to take standard antibiotic treatment throughout the study period.

Life-threatening bacterial or fungal infections developed in only half as many gamma-interferon patients compared with placebo recipients, the team found. Children under age 10 seemed to benefit the most from the treatment: 81 percent of those receiving interferon remained infection-free one year later, compared with 20 percent on placebo.

Scientists have speculated that gamma interferon can spur phagocytes to release increased amounts of superoxide anion. The new study failed to verify that mechanism, but Gallin says his own, unpublished results show that phagocytes obtained from the blood of gamma-interferon patients show enhanced fungus-killing ability in the test tube. Even if in vivo experiments eventually confirm this phagocyte-boosting prowess, many scientists now suspect that the drug somehow bolsters the immune system in a more general way, potentially offering a new treatment avenue for other types of immunity-decimating conditions.

The Food and Drug Administration, privy to early results from the international trial, approved gamma interferon for treatment of CGD last December. That action and the findings released this week provide new hope for families coping with the inherited disease.

At the same time, the prospect of lifelong gamma-interferon treatment for people with CGD raises safety concerns, especially for infants and children. The drug's manufacturer, Genentech, Inc., of South San Francisco, plans another trial to determine the long-term effects of administering the drug to growing children, says Howard S. Jaffe, Genentech's director of clinical research.

For many CGD sufferers, life resembles a roller coaster, bringing terrifying bouts of illness between runs of good health. "When these people feel that there is some hope, it's a wonderful thing," says Heather Karp of Rockville, Md., whose two college-age sons have CGD and have begun taking gamma interferon.
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Title Annotation:drug to treat infections in people with chronic granulomatous disease
Author:Fackelmann, Kathy A.
Publication:Science News
Date:Feb 23, 1991
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