The hunt for new treatments against H5N1 avian flu must focus on drugs that prevent the massive inflammation the virus causes, experts say.

The warning follows details from the first-ever controlled clinical study of the virus's immunological effects.

Vietnamese doctors who treated 18 victims of H5N1 infection in 2004/5 have documented in the latest issue of Nature Medicine how their patients’ immune systems became stoked up to an extraordinary degree.

Their comparison of the patients, 13 of whom died, with eight others suffering normal H3N2 or H1H1 human influenza, revealed the extent of immune-dysfunction.

Most strikingly, they observed a massive release of inflammatory cytokines and chemokines, chemicals that rev-up the immune system, causing huge inflammation and tissue damage. Some of these substances were present at levels hundreds or thousands of times higher than in patients with ordinary influenza.

These observations explain how H5N1 infection typically kills patients through pneumonia and multi-organ failure, the researchers say.

The focus of new drug development and clinical management "must be in preventing this intense cytokine response,” said the lead investigator Dr Meno de Jong of the Oxford University Clinical Research Unit at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam.

His team reported in Nature Medicine that the patients who died from H5N1 had the highest levels of cytokines - and the highest levels of virus - circulating in their bodies. The results also underlined the need to provide anti-viral drugs very quickly, he said. Once the cytokine burst had started it was usually too late to alter the course of the disease.

Another important discovery was that, conversely, one component of the immune system, the T-cell response, was fatally weakened by H5N1 infection, thereby allowing viral replication to increase.

Dr Wendy Barclay, a virologist at Reading University who studies the effects flu viruses on the immune system, said: “The research suggests that stopping the virus replicating early on infection with antivirals in the key to treatment.”

She noted that treating patients with anti-inflammatory drugs, as some doctors have suggested, “might do more harm than good”. “Immunomodulatory drugs are blunt instruments. The last thing you want to do is weaken parts of the immune system needed to fight the virus.”