Body's misguided immune response may cause harm in SARS infection

Thursday, May 15th 2003, 12:00 am

By: News On 6

Much of SARS victims' life-threatening lung damage appears to result from an overly aggressive counterattack by their own bodies, suggesting that virus-killing drugs alone may fail to stop the disease.

Researchers are testing drugs already on the shelf and creating new ones in an effort to find something that will destroy the virus and arrest the disease, which can wreck the lungs. However, many worry that the body's own attempt to fight off the virus is part of the problem, and a study released Thursday supports that concern.

Researchers examining victims' lungs found two sources of damage: the virus itself and the white blood cells summoned to fight it. This combination of offense and misguided defense plays a part in many infectious diseases, and the researchers said finding it so prominently in SARS supports the strategy of subduing patients' immune systems to help them get better.

In fact, some doctors treating SARS in Hong Kong and elsewhere already routinely give steroid drugs to patients to restrain their immune defenses and protect them from a flood of potentially harmful chemicals, called cytokines, aimed at the virus. However, this approach is controversial, and some question whether it could do more harm than good by dulling patients' virus-fighting edge.

The latest evidence, based on lung samples taken from six people who died of SARS, was released on the Internet on Thursday by the British journal Lancet. The study was conducted by Dr. John M. Nicholls and others at the University of Hong Kong.

No drugs are proven to kill the SARS virus inside the body. However, with nothing else to offer, some doctors have used a combination of ribavirin, which works against some other respiratory infections, and steroids.

Enthusiasm for ribavirin has waned, especially after lab tests found no sign it kills the virus. And some doctors said the latest study should not prompt further use of steroids, at least until there is evidence in animal studies that the approach improves recovery.

``With a few patients, you cannot make those kinds of recommendations,'' said Dr. Sherif Zaki, pathology chief at the U.S. Centers for Disease Control and Prevention. ``You are dealing with human life. You have to have evidence.''

The debate also went on in this week's issue of the New England Journal of Medicine, which published five SARS reports released earlier on the Internet. Dr. Yuji Oba of the University of Missouri in Kansas City wrote a letter calling steroids potentially hazardous in SARS, while Drs. Nelson Lee and Joseph Sung of Chinese University of Hong Kong responded that the treatment has been given ``to suppress the cytokine storm ... and, in fact, in many cases, it did.''

The Lancet report showed evidence of extensive destruction triggered by blood cells called macrophages. These cells produce a variety of chemicals that fight infection but also trigger dangerous inflammation.

The doctors said some of the resulting lung damage is similar to what was seen in the bird flu outbreak, which killed several people in Hong Kong in 1997. They said this suggests that large amounts of inflammatory chemicals produced by macrophages in the air sacs of the lungs help explain why both diseases can be lethal.

``If this is true, it's possible one could intervene at the very early stages of SARS and use anti-inflammatory agents,'' such as steroids and other immune-suppressing drugs, said Dr. Zab Mosenifar, pulmonology chief at Cedars-Sinai Medical Center in Los Angeles.

However, he and several other doctors said they would be reluctant to suppress patients' immune defenses unless they could also give them effective virus-fighting drugs.

Dr. Michael Worthington, chief of infectious diseases at Caritas St. Elizabeth's Medical Center in Boston, noted that a variety of sudden, untreatable lung infections cause damage ``that looks a lot like this. It's hard to show a benefit of steroids, and sometimes they are harmful.''