September 3, 2004
Long-Term Effects of Carbon
Are An Autoimmune Reaction
Study Has Implications for Prevention of
Brain Damage After Exposure
(Philadelphia, PA) - Later this fall, emergency-medicine
physicians enter into what they call the “CO season”
- a time when faulty furnaces and other mechanical mishaps
lead to a spike in cases of carbon monoxide (CO) poisoning.
CO poisoning is the leading cause of injury and death
by poisoning worldwide, with about 40,000 people treated
in the U.S. annually. Brain damage occurs - days to
weeks later - in half of the patients with a serious
case of CO poisoning.
The physiological causes of this delayed decline were
not well understood until now. A team led by Stephen
R. Thom, MD, PhD, Professor of Emergency Medicine
and Chief of Hyperbaric Medicine, at the University
of Pennsylvania School of Medicine, report
this week online in the Proceedings of the National
Academies of Sciences that CO causes profound changes
in myelin basic protein (MBP) - a major protein constituent
of myelin, the protective sheath surrounding neurons.
Using an animal model, they showed that the CO-induced
changes in MBP set into motion an autoimmune response
in which lymphocytes, triggered to eliminate altered
MBP, continue to attack normal MBP.
Specifically, the researchers found that by-products
of CO metabolism in the brain alter the charge and structure
of MBP. “These changes in MBP have also been demonstrated
in multiple sclerosis, which is why we paralleled the
study along those lines,” says Thom.
To link acute CO poisoning to long-term brain injury,
the team conducted tests on normal versus CO-poisoned
rats, comparing their abilities to navigate and memorize
a maze. "CO poisoned rats don't learn," said
Thom. "But if you render their immune systems tolerant
to altered MBP, by feeding them normal MBP before CO
poisoning and thereby short-circuiting the lymphocyte
response, the rats learn normally."
Thom says that overall this work suggests that the 50
percent or more of patients who develop brain damage
following severe CO poisoning may do so, in large part,
due to an autoimmune reaction. The body simply does
not know when to stop attacking what it now views as
an invader. “This opens up a lot of possibilities,
such as treatment with immunosuppressant agents, in
conjunction with standard hyperbaric oxygen therapy,”
he says. “Until our study elucidated this immune
response, we had no motivation to think along those
Penn colleagues on the paper are: Veena M. Bhopale,
Donald Fisher, Jie Zhang, and Phyllis Gimotty. This
study was funded by the National Institutes of Health.
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