New evidence of cytokine storm in avian flu cases

Jun 14, 2006 (CIDRAP News) – Scientists in Hong Kong have reported new experimental evidence that avian influenza infections in human cells are more likely to trigger a destructive immune-system overreaction, or "cytokine storm," than human flu viruses are.

Writing in the July 1 Journal of Infectious Diseases, the researchers report that two avian flu viruses, a 1997 strain of H5N1 and a 1997 H9N2 strain, caused immune system cells in lab cultures to produce much greater levels of certain chemokines (a class of cytokine, or messenger protein) than such cells did when infected with an ordinary human flu virus.

"In general, the chemokines and chemokine-receptor responses of MDMs [monocyte-derived macrophages, a type of immune cell] to avian influenza viruses were much stronger than those to human virus, which may account for the high pathogenicity of avian viruses," the report states.

In addition, the H5N1 strain caused immune cells from adults to produce higher levels of certain cytokines than similar cells from newborn babies did. The authors say that finding may help explain why Hong Kong's human H5N1 outbreak in 1997 killed 5 of 9 infected adults (older than 12) but only 1 of 9 infected children. That sharp difference in adult and child mortality rates has not been seen in the current wave of H5N1 cases dating to late 2003.

Scientists have suggested that the cytokine storm played a role in the high death rate in the 1918 Spanish flu pandemic and is playing a similar role in human cases of H5N1 infection today. Autopsies of H5N1 avian flu victims in Vietnam and elsewhere have revealed lungs choked with debris from excessive inflammation triggered by the virus. Similar severe lung damage was frequently reported in victims of the 1918 pandemic, which disproportionately killed people with the strongest immune systems—young, healthy adults.

The new study was conducted by a University of Hong Kong team that has previously reported experimental evidence of a cytokine storm in H5N1 avian flu. The team includes J. S. Malik Peiris and, as first author, Jianfang Zhou.

In view of the severe lung damage caused by H5N1 in humans, the team decided to measure the expression of four chemokines and two chemokine receptors induced in MDM cells by avian and human flu viruses. They also sought to compare the chemokine production induced by these viruses in adult-derived MDMs and in neonatal MDMs derived from umbilical cord blood.

Three viruses were used: a strain from the 1997 human outbreak in Hong Kong, a 1997 strain of H9N2 from quail, and a 1998 strain of H1N1 human flu from Hong Kong. The H9N2 virus is a precursor of the H5N1 virus, with which it shares six internal proteins, the report says. Because of the safety risks involved in working with H5N1 viruses, the team first did the experiment with the H9N2 virus and then repeated it with the H5N1 virus in a biosafety level 3 facility.

See also:

Nov 16, 2005, CIDRAP News story "Lab study supports idea of 'cytokine storm' in H5N1 flu"

Center for Infectious Disease Research & Policy
Academic Health Center -- University of Minnesota
Copyright © 2006 Regents of the University of Minnesota

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