[CO-CURE] Avian flu--What can we do about it?

[Guest guest]

Hi, all.

As you may know, the mortality rate for the H5N1 avian flu in humans so far

has been running at around 50%.  As you also probably know, cases of avian flu

have been showing up recently in Asia that are resistant to the drug Tamiflu. 

Since we don't yet have a stockpile of vaccine against this flu, this leaves

the population of the world very vulnerable, should the virus mutate into

having the capability of human-to-human transmission and develop into a

pandemic. 

Is there anything we as individuals can do to protect ourselves and others,

should this occur?

Studies on the kill mechanism of this virus have revealed some interesting

results.  The primary target cells for this virus are the epithelial cells

lining the alveoli (air sacs) in the lung (Ebisawa et al. Am Rev Respir Dis

1969,

99:507-15).  The work of the group at the University of Hong Kong has shown

that while the replication  efficiency of the H5N1 flu virus is no greater than

that of less virulent human flu viruses, the H5N1 virus provokes a much

stronger cytokine response from both macrophages (Cheung et al., Lancet 2002,

360(9348):1801-2) and epithelial cells (Chan et al., Resp Res 2005, 6:135).

According to Chan et al, citing earlier references from their group and

others, " Most patients with H5N1 disease had a primary viral pneumonia

complicated

by the syndromes of acute respiratory distress and multiple organ dysfunction

with lymphopenia and hemophagocytosis being notable findings. "

Based on this, it appears that in avian flu the immune system over-responds. 

There is a very large cytokine output, and this stimulates immune cells,

probably macrophages in particular, to generate large amounts of reactive oxygen

species.  Normally, the main protection for the lung's epithelial cells against

damage by oxidizing species is known to be the high concentration of

glutathione in the epithelial lining fluid.

In view of the evidence, I think that in fatal cases of avian flu the high

production of reactive oxygen species is sufficient to overcome this antioxidant

protection.  The result is depletion of glutathione in the lungs, damage to

the epithelial lining of the alveoli, intrusion of fluid into the lungs 

(producing the respiratory distress), and finally depletion of glutathione in

other

organs as the lungs draw on their supplies, producing the multiple organ

dysfunction and death.

If this mechanism is in fact what takes place, then it seems to me that

providing the substrates for making glutathione (such as N-acetylcysteine), or

better yet, providing aerosol glutathione directly to the lungs by nebulizer,

should be considered as approaches to dealing with cases of avian flu.

I am not the first to suggest boosting antioxidants in avian flu, but I do

think it's a good idea.  Comments would be welcome.

Rich Van Konynenburg, Ph.D.