New flu treatment calms immune response
Hopes for human drug raised as damaging inflammation curbed in
mice.
23 October 2003
JOHN WHITFIELD
Researchers in Britain may have invented a new way to treat flu.
Promising results in mice could lead to human trials.
The therapy dampens the body's response to infection. It might also work
for other diseases in which our defences overreact, such as asthma or multiple
sclerosis, says one of its developers, Tracy Hussell of Imperial College,
London. "There are many situations where the immune system goes mad," she
says.
Unlike vaccines or antivirals, the new drug attacks the symptoms of flu
rather than the virus itself. So it should be unaffected by strains that mutate
to dodge more direct attacks.
"It clearly has potential," says immunologist David Gray of the
University of Edinburgh. Similar anti-inflammatory drugs are already used to
treat rheumatoid arthritis, he says, but other options would be welcome: "One
could have a whole range of these drugs to pick off the shelf for a particular
disease."
The researchers studied mice infected with influenza A. This strain
caused the Spanish flu pandemic of 1918-19, which killed more than 20 million
people worldwide.
There is no guarantee that the drug will work in humans. "Flu isn't a
natural infection of mice," warns influenza expert Alan Hay of the National
Institute for Medical Research in London. "But it's certainly something worth
following up," he says.
Enemy within
A body with flu can be its own worst enemy. Immune sentries called T
cells rush to the lungs, releasing chemicals that cause inflammation. This can
be life-threatening: it blocks blood vessels cutting off the body's oxygen
supply.
It is not clear why we mount such a counterproductive defence. It may be
that the deep recesses of our lungs are unaccustomed to foreign bodies, and so
respond with unusual vigour.
Hussell's team stops these overzealous T cells loitering in the lungs.
Their treatment blocks a molecule on the cells' surface called OX40. Normally,
OX40 is switched on about two days after a T cell meets the flu virus,
prolonging the cell's life. The protein that blocks OX40 was originally
developed to treat inflammatory bowel disease.
The drugged body can still defend itself. T cells stream into the lungs,
but not in numbers that cause severe inflammation. The cells are efficient
virus-killers in the two days before they switch on OX40, and those that have
not encountered flu carry on as normal.
Infected mice normally lose a quarter of their body weight, and become
feverish. A drug dose three days after exposure kept them healthy1. "They didn't look infected at all," says Hussell.
Wrong diagnosis should not be a problem, Hussell adds. Common cold
viruses produce the same immune response, and the treatment should work just as
well.
The researchers are seeking funding for a clinical trial in healthy
humans and, if that goes well, in asthmatics. Barring any setback, a drug is
five to ten years away.
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