Bird Flu Triggers Immune System 'Storm'

H5N1 virus spurs massive, and potentially deadly, inflammatory reaction, scientists say

FRIDAY, Nov. 11, 2005 (HealthDay News) -- As concern mounts over the potential spread of avian flu to humans, researchers believe they've discovered one reason why the infection can prove so deadly.

Experiments with human cells have found the H5N1 virus can trigger levels of inflammatory proteins called cytokines and chemokines that are more than 10 times higher than those that occur during a bout of the common flu.

This massive increase in cytokine and chemokine activity can inflame airways, making it hard to breathe. It also contributes to the unusual severity of the avian flu, which can result in life-threatening pneumonia and acute respiratory distress.

According to the latest World Health Organization data, 125 cases of human H5N1 infection have been reported worldwide, including 64 deaths. All of these cases have occurred in Southeast Asia, and involved bird-to-human transmission. However, experts warn that if the virus mutates so that it can pass from human to human, a global pandemic could ensue.

Reporting in the Nov. 11 online edition of Respiratory Research, Michael Chan from the University of Hong Kong and his collaborators in Vietnam looked at the levels of cytokines and chemokines in human lung tissue exposed to the H5N1 virus.

They compared protein levels induced by strains of the H5N1 virus with levels induced by a more common, less virulent human flu virus, called H1N1.

Chan's team found that H5N1 induces more pro-inflammatory proteins than H1N1. After infection with H5N1, levels of the chemokine IP-10 in bronchial epithelial cells reach 2200 picograms per milliliter , compared with only 200 picograms per milliliter in cells infected with H1N1. Similar results were found for levels of other chemokines and cytokines.

"The recent re-emergence of H5N1 disease in humans is a cause for renewed pandemic concern and highlights the need for a better understanding of the pathogenesis of human H5N1 disease," the study authors wrote. "Such understanding will lead to new strategies for managing human H5N1 disease and enhance our preparedness to confront pandemic influenza, whether from H5N1 or other influenza A subtypes."

One expert said the findings are in line with symptoms seen so far in patients infected with the avian flu strain.

"These findings fit with what we see clinically," said Dr. Christian Sandrock, an assistant professor of pulmonary critical care and infectious diseases at the University of California Davis. "This is what we would expect with this virus."

When the H5N1 virus comes into contact with the cells of the trachea and small air sacs in the lungs, it drives up the production of these cytokines, Sandrock explained. The cytokines trigger inflammation, a normal response by the body to help fight the virus.

"The problem is that sometimes the inflammation can be so bad there's collateral damage," he said. "That collateral damage can cause inflammation and damage to your lungs enough so that you are unable to breathe, and you get acute respiratory distress."

The findings provide a scientific reason for what is being seen clinically, Sandrock said. "But there's still a lot we don't know," he added.

"This study confirms earlier work that H5N1 induces a cytokine 'storm,'" said Michael T. Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota School of Public Health, in Minneapolis. "It helps us understand the pathophysiology of the disease."

The noted increase in cytokine production is what distinguishes avian flu from other flu, Osterholm said. "The hyperproduction of cytokines is very relevant. It points out that the way people actually experience severe illness with this virus is different than what we see with other influenza viruses."

"This is basically a cytokine storm induced by this specific virus, which then leads to respiratory distress syndrome," Osterholm said. "This also makes sense of why you tend to see a preponderance of severe illness in those who tend to be the healthiest, because the ability to increase the production of cytokines is actually higher in those who are not immune-compromised. It's more likely in those who are otherwise healthy."

More information

Find out more about avian flu at the U.S. Centers for Disease Control and Prevention.

SOURCES: Michael T. Osterholm, Ph.D., professor, public health, and director, Center for Infectious Disease Research and Policy, University of Minnesota School of Public Health, Minneapolis; Christian Sandrock, M.D., M.P.H., assistant professor, pulmonary critical care and infectious diseases, University of California, Davis; Nov. 11, 2005, Respiratory Research online
Consumer News