Monday
April 3, 2006
news@michigandaily.com

SCIENCE

5A

5A

Inside the lungs:

NG
GRAPHIC: GERVIS MENZIES
proteins and

B I O L O G I CsAyL
CIVIL WAiR
Battling the body's immune system

'U' researcher
investigates causes of
overactive inflammatory
systems
By Deepa Pendse
Daily Science Writer
Imagine a war in which one of
the armies becomes so dominant
that it starts to attack its own coun-
try. An overactive immune system
works much like that - attacking
the body it is designed to protect.
Medical School Prof. Peter Ward
who works in the University's
Pathology Department, is research-
ing the inflammatory response to
better understand how to control an
overblown response.
The immune system, specifi-
cally the inflammatory response,
is often called the "first line of
defense" against invading bacteria
and viruses. Inflammation is the
movement of fluid, important pro-
teins and white blood cells to the
site of infection. But when inflam-
mation becomes uncontrollable, it
sometimes attacks a patient's own
body. Many illnesses are caused by
a hyperactive immune system. One
such illness is sepsis, an exagger-
ated immune response to a bacterial
or viral infection, which can lead
to loss of limbs, shut down organs
and may even lead to death. An
overactive inflammatory response
can also result in rejection of organ
transplants
Ward's work focuses on inflam-
mation in the lungs, which are more
susceptible to an overactive inflam-
matory response than other organs.
One of the main areas of his
research is the role of cytokines and

chemokines,
small pro-
tein "mes-.
sengers"
that trigger
the inflam-
matory
response, in
the immune
response
pathway._W.rd>
Ward said Ward
very little
is known about the origin of these
protein messengers, or which ones
are important.
Other key players in the inflam-
matory response are complement
proteins, a system of 30 proteins
that interact to control the immune
.system, and trigger the inflamma-
tory response. Complement pro-
teins make a logical target for his
research because by blocking them,
scientists can cut off the chain reac-
tion that triggers the inflammatory
response at its initial stage.
One of Ward's research projects
concerns a complement protein
called C5. This protein is likely to
have a role in the cause of sepsis.
Ward and his research team have
found that by blocking C5 recep-
tors, the inflammatory response is
greatly reduced.
Ward said 600,000 to 800,000
people develop sepsis every year and
around 30 to 50 percent of them die.
Sepsis also takes a heavy economic
toll, costing patients in the U.S. alone
$18 to 20 billion per year.
So far the only effective drug to
treat sepsis is produced by Eli Lilly,
a leading pharmaceutical company.
The drug, Xigris, uses a protein
with anti-inflammatory effects,
called Activated Protein C.
According to the company,

Xigris is much more cost-effective
than traditional sepsis therapy. But
Ward criticized the effectiveness
of Xigris, pointing out that use of
the drug caused the mortality rate
to improve only marginally, falling
to a rate of 28 to 32 percent. The
company is currently continuing
research on the effects of Activated
Protein C.
According to Medical School Prof.
Theodore Standiford, about 325 to
350 patients were diagnosed with
sepsis at the University's hospital last
year. Standiford also noted that while
the incidents of sepsis were increas-
ing because of an aging population,
more invasive medical procedures
and more aggressive immunosup-
pressive therapy, the mortality rate
for sepsis was decreasing.
Some University doctors pre-
scribe Xigris to treat patients with
severe sepsis. In 2005, 16 patients
received the treatment. University
doctors have strict guidelines to fol-
low when prescribing Xigris. It can
only be given to patients who are at
a severe stage of sepsis. In the mild-
er stage, Xigris can actually harm
the patient rather than help. Stud-
ies have shown that in less severe
patients Xigris is correlated with
a two-fold increase in intercranial
bleeding, Standiford said.
In the face of diseases such as sep-
sis, Ward said better understanding
of the inflammation pathway and
the immune system seems urgent.
Researchers haVe come a long way
since the discovery of chemokines
20 years ago, but that there is still
progress to be made. Ward said he
hopes the scientific community will
be able to provide effective drugs
within the next five to 10 years to
battle sepsis and other overactive
inflammatory diseases.

Fast facts about the immune system

The inflammatory response is the movement
white blood cells to the site of infection.

of fluid, importantr

An overactive inflammatory response can cause damage to the body.
Sepsis, an exaggereated immune response to a bacterial or viral infection,
can cause the loss of limbs, organ malfunction and even death.
Diseases like those shown in the lung on the right, can trigger an overactive
inflammatory response. Lungs are more susceptible to an overactive inflamma-
tory response than other organs.


If you're a junior, senior or a grad student, you could be one of the lucky
seven selected for an all-expenses-paid one-day internship with one of
these Michigan success stories:
W PFF Hurry', Deadlint
" David Brandon, '74, CEO,
Domino's Pizza, Inc. p i $A
Location: Ann Arbor, Michigan
0 Randy and Jason Sklar, '94, comedians, hosts of ESPN Classic's "Cheap Seats"
Location: New York, New York
* Joe Schwarz, '59, HLLD'03, member of United States House of
Representatives, representing 7th district of Michigan
Location: Washington, DC
* Aaron Dworkin, '97, MMUS'98, founder and president of Sphinx Organization
for minorities in the classical arts
Location: Ann Arbor, Michigan
* Harvey Briggs,'82, executive vice president and director of innovation for
Lindsay, Stone & Briggs
Location: Madison, Wisconsin
* Linda McFall, '89, senior editor of Mira Books

(a division of Harlequin books)
Location: New York, New York

t~w