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Chronic Sinusitis Sufferers Have Enhanced Immune Responses to Fungi
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.

Reference: S-H Shin et al. Chronic rhinosinusitis: An enhanced immune
response to ubiquitous airborne fungi. The Journal of Allergy and
Clinical Immunology. Published online Oct. 8, 2004. doi:
10.1016/j.jaci.2004.06.012.