Chronic Sinusitis Sufferers Have
Enhanced Immune Responses To Fungi
October 8, 2004 -- Scientists supported by the National Institute of
Allergy and Infectious Diseases (NIAID), part of the
National
Institutes of Health, have discovered that people with
chronic sinus inflammation have an exaggerated
immune
response to common airborne fungi. The results of their
study appear online today in The Journal of Allergy and Clinical
Immunology.
"This study is the first to show a possible immunologic basis for
chronic
sinusitis, an important starting point to better
understand the etiology of the illness," says Marshall Plaut, M.D., chief
of NIAID's
allergic
mechanisms section. Despite the enormous
health
impact of chronic sinusitis--nearly 30 million people were diagnosed with
sinusitis
in 2002, according to U.S. Centers for Disease Control and Prevention, and
direct costs of the illness exceed $5.6 billion per year--the condition is
very poorly understood, he says.
The researchers, led by Hirohito Kita, M.D., of the Mayo Clinic in
Rochester , MN , compared blood samples taken from 18 people diagnosed
with chronic sinusitis with blood samples from 15 healthy volunteers.
Nasal secretions from the two groups were also examined for the presence
of fungal proteins and inflammation-causing immune system molecules.
Airborne microscopic fungi spores abound indoors and out. People may
inhale a million or more fungal spores each day, notes Dr. Kita. The mere
presence of such fungi in the airways, however, is not enough to cause
sinusitis because these spores can be found in the upper respiratory
tracts of both sinusitis sufferers and non-sufferers. Indeed, in this
study, levels of fungal proteins in nasal secretions were similar in both
groups.
The Mayo Clinic scientists looked for evidence that people with sinusitis
respond abnormally to these harmless fungi. The investigators exposed
immune cells derived from the blood samples to extracts of four common
airborne fungi: Alternaria, Aspergillus, Penicillium and Cladosporium. The
cells of chronic sinusitis sufferers released significant amounts of three
immune-modulating chemicals, called cytokines, specifically
interferon-gamma, interleukin-5 (IL-5) and IL-13. In contrast, cells from
healthy volunteers released very little interferon-gamma and no IL-5 or
IL-13. The most dramatic responses occurred after exposure to Alternaria.
Importantly, says Dr. Kita, the released cytokines represent both major
classes of cytokines--interferon-gamma is in the Th1 group and IL-5 and
IL-13 are in the Th2 class. This is notable because scientists have
thought that allergic reactions involve only Th2 cytokines, Dr. Kita
explains. (While chronic sinusitis is not considered to be an allergic
disease, people with the condition also often have asthma and allergic
rhinitis, giving scientists reason to suspect a link.) The current
findings add to an evolving understanding of allergic diseases that
suggests symptoms may stem from a combination of Th1 and Th2 cytokines.
The combined effect of excess Th2 and Th1 cytokines released in the
presence of fungi may explain a number of chronic sinusitis symptoms,
including persistent inflammation of sinus and nasal mucous passages, say
the scientists.
Previously, Mayo clinic scientists used intranasal antifungal agents to
successfully treat patients with chronic sinusitis. While those studies
generated controversy, in part because other researchers were unable to
replicate the findings, Dr. Kita says today's report supports the
rationale of treating chronic sinusitis with antifungals. Clinical trials
to further test antifungal therapy for chronic sinusitis are being
planned, adds Dr. Kita.
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NIAID is a component of the National Institutes of Health, an agency of
the U.S. Department of Health and Human Services. NIAID supports basic and
applied research to prevent, diagnose and treat infectious diseases such
as HIV/AIDS and other sexually transmitted infections, influenza,
tuberculosis, malaria and illness from potential agents of bioterrorism.
NIAID also supports research on transplantation and immune-related
illnesses, including autoimmune disorders, asthma and allergies.
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