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