# 987
The big news of the past 24 hours has been the study released by Dr. Robert Webster and St. Jude's Medical Research Hospital on the effects of down regulating the immune system in H5N1 infections. This study, done in mice, appears to invalidate the idea that the high mortality rates seen with the H5N1 virus are due to the over production of cytokines.
Of course, that still leaves some unanswered questions. Like, why does the virus seem to overwhelm younger, healthier people? And how does this mesh with earlier studies that suggested an overwhelming immune response?
CIDRAP (Center for Infectious Disease Research and Policy) News is carrying a somewhat contrarian report today.
Study: Inhibiting cytokine response might not reverse H5N1 infections
Lisa Schnirring
Staff Writer
(Excerpt)
However, an internationally known virologist who discussed the study's findings with CIDRAP News and asked not to be named disagreed with the authors' conclusions, but said their data were important.
Cytokine cascades are pleiotropic and multiply redundant, and once one starts, it is unlikely that blocking a single cytokine will have a major effect, the virologist said.
"Thus, these results do not disprove a role for cytokines in the pathogenesis of H5N1," said the expert, though the data may support the argument that therapy to block a single cytokine may not be clinically beneficial.
The virologist pointed out that mice with TNF receptor defects lost less weight than the wild-type mice (9.1% vs 17.1%), though the difference may not be statistically significant because there were only three mice in each study group. The scientist also said the glucocorticoid-treated mice lost less weight than the untreated group.
"If inflammatory responses are not contributing to pathology, how is glucocorticoid therapy having such a strong effect on weight loss?" the virologist asked.
Mortality patterns in the mice are not unexpected, the expert said, noting that in mice the H5N1 virus primarily kills by neuroinvasion rather than by respiratory pathology.
"In any event, these data cannot be ignored, nor can it be concluded that these results refute the role for cytokines in the pathogenesis of human H5N1 lung disease," the virologist commented. "The role of inflammatory responses in the pathogenesis of influenza is still far from understood."
This article also quotes Dr. Michael Osterholm, who also calls the conclusions into question.
Fortunately, I'm not qualified to weigh in on either side of this issue. All I can do is report both arguments. Suffice to say there will need to be more research done on this issue before it can be resolved.
The PNAS Journal article is now available online here.
