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
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
News releases, fact sheets and other NIAID-related materials
are available on the NIAID Web site at http://www.niaid.nih.gov.
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.