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National Institute of Allergy

and Infectious Diseases (NIAID)

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FOR RELEASE

Tuesday, October 12, 2004

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Anne A. Oplinger

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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.

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.

News releases, fact sheets and other NIAID-related materials are

available on the NIAID Web site at http://www.niaid.nih.gov.

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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.