(NIAID)Chronic sinusitis sufferers have enhanced immune responses

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Chronic sinusitis sufferers have enhanced immune responses to fungi

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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.