Dr. Andy

Reflections on medicine and biology among other things

Monday, November 14, 2005

Avian flu and cytokine storm

This article (via Instapundit) describes the effects of the H5N1 avian flu virus on lung tissue in culture

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 original article, in PDF form is here.

As advertised, the report does show an increase in some cytokines and chemokines (cytokines are small soluble signaling molecules that carry messages from one cell to another and chemokines are similar molecules that help direct the migration of inflammatory cells to where they are needed). Basically what they did is infect cultures of cells from human lung with different strains of influenza and then measure production of various chemokines and cytokines. They performed the important control of showing that both avian and "regular" influenza virus replicated similarly in the cells. How important the differences in these signaling molecuse are is not clear. I wouldn't worry much about it except that it seems to replicate the clinical experience seen with H5N1 infection of humans.

The clinical experience with H5N1 is that it does generate severe lung pathology with an overexuberant amount of inflammation. This leads to the lung filling with fluid and debris which makes it increasingly hard to breathe. Most deaths from avian flu have been from respiratory failure. What you want with any infection is a medium amount of inflammation to recruit inflammatory cells to fight it off, but not so much that it starts being detrimental to normal organ function.

As to Glenn's idea of using inhaled steroids, I'd say it is not bad for a law professor. Definitely better than I could do in, say, discussing the establishment clause and prayers at high school football games. Steroids will fight inflammation and may decrease morbidity in conditions with overwhelming inflammation. They've been tried empirically in patients with avian flu with mixed success.

Corticosteroids have been used frequently in treating patients with influenza A (H5N1), with uncertain effects. Among five patients given corticosteroids in 1997, two treated later in their course for the fibroproliferative phase of ARDS survived. In a randomized trial in Vietnam, all four patients given dexamethasone died
They were also used empirically in SARS, again with uncertain benefit (when a doctor says he wants to try something "empirically" it basically means he/she ha no idea if it will work or not). Empiric use of steroids in critically ill patients is common, an onc fellow once noted "nobody goes down without steroids," but studies have suggested they are only beneficial in the general population of critically ill patients in low doses and to the extent that the patient's production of endogenous steroids is compromised, with no additional benefit from higher, anti-inflammatory doses.

The benefit of inhaled steroids in asthma is not that they work better, they don't, but that it decreases the side effects (decreased growth, decreased bone density, etc) that occur with prolonged use of steroids. When patients with asthma have acute exacerbations and go to the ED, they get systemic steroids. In an acute infection like influenza I'd want to maximize efficacy by giving the steroids systemically (oral or via IV) and wouldn't worry much about the side effects since they'd only be used for a short time (and because the patient is presumably so sick).


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