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New Approach to Treating Childhood Ear Infections Discussed in Two Articles by House Ear Institute Researchers

Scientists Address Possible New Approaches to Treating the Epidemic Problem of Otitis Media

LOS ANGELES - July 20, 2004 - Research scientists in the House Ear Institute's Department of Cell and Molecular Biology recently published articles on findings from two separate research studies of middle ear infections, or otitis media (OM). Both studies aim to identify targets for new treatments for ear infections, which after the common cold, are the second most common ailment affecting children age eight and younger. Otitis media accounts for more than 31 million visits to the doctor each year in the U.S., and is cited as the most frequent reason for taking children to the emergency room.

Current treatment for middle ear infections is antibiotic therapy, sometimes in repeated courses, to discourage recurring infections. This treatment method has been used over the past three decades, resulting in a dramatic worldwide emergence of antibiotic-resistant bacteria. This has led to a reduction of the number of effective antibiotics for OM and has begun to pose a major public health threat. HEI researchers are studying the pathological processes underlying otitis media to identify potential therapies that can combat the specific bacteria causing infection, and boost the body's innate immunity to the disease.

A paper co-authored by HEI researcher Jian-Dong Li, M.D., Ph.D., in the March 2004 issue of Proceedings of the National Academy of Sciences (PNAS), focused on understanding the process of inflammation - recently identified as a hallmark of other diseases like lung infection, heart disease and cancer - in the pathogenesis of middle ear infections. The article, titled "Synergistic Activation of NF-kB by Nontypeable Haemophilus influenzae [NTHi] and Tumor Necrosis Factor" explains how most studies focus on understanding how inflammation is caused by a single inducer at a time, while the HEI study examines how multiple inducers cause bacteria-induced inflammation simultaneously, since multiple inducers co-exist in patients in vivo.

This study for the first time shows that NTHi, a common bacterial pathogen in otitis media in children and chronic obstructive pulmonary disease (COPD) in adults, cooperates with TNF-a, a common cytokine, to synergistically induce inflammation through activation of NF-kB (a transcription regulator) via signaling pathways. This work should elucidate the molecular mechanisms underlying the combinatorial regulation of inflammation and lead to development of therapeutic strategies for NTHi-induced infections. Co-investigators on this study are David J. Lim, M.D., Hirofumi Jono, Ph.D., and Takahiro Watanabe, M.D., at HEI, and Jiahuai Han, Ph.D., at the Department of Immunology, The Scripps Research Institute.

A second otitis media paper from HEI takes a different approach to solving the disease, and was published in the May 2004 issue of BMC Infectious Diseases. David Lim, M.D., was the senior author, and Haa-Yung Lee, Ph.D., the first author of an article titled "Antimicrobial Activity of Innate Immune Molecules Against Streptococcus pneumoniae, Moraxella catarrhalis and nontypeable Haemophilus influenzae [NTHi]," which discusses the function of innate immune molecules as defenders against pathogens to protect the host. That is, these naturally occurring molecules constantly survey the body in order to clear it of opportunistic microorganisms that can cause ear infections. The aim of this study is to understand the role of innate immune molecules in the normal defense and maintenance of the middle ear, in order to potentially boost the body's natural defense - and its own antibiotics - against bacterial infection.

This study shows that locally-produced lysozyme and certain defensins can inhibit the growth of clinical isolates of OM pathogens and cause ultrastructural damage to them, indicating that select components of innate immunity constitute the first line of defense against infection. The study was conducted in HEI's Section of Pathogenesis of Ear Diseases, Department of Cell andMolecular Biology, led by David Lim, M.D. Co-authors for this paper were Ali Andalibi, Ph.D., Paul Webster, Ph.D., Karen Teufert, M.D., and Jian-Dong Li, M.D., Ph.D., Sung-Kyun Moon, M.D., Ph.D., Sung-Ho Kang, M.D., Ph.D., at HEI and Tomas Ganz, M.D., at Department of Medicine, University of California, Los Angeles (UCLA).

About the House Ear Institute

The House Ear Institute (HEI) is a private, non-profit 501(c)(3) organization dedicated to advancing hearing science through research and education to improve quality of life. Established in 1946 by Howard P. House, M.D., as the Los Angeles Foundation of Otology, and later renamed for its founder, the House Ear Institute has been engaged in the scientific exploration of the auditory system from the ear canal to the cortex of the brain for more than 55 years.

Our scientists continue to explore the developing ear and ear diseases at the cell and molecular level, as well as the complex ear-brain interaction. They are also working to improve hearing aids and auditory implants, diagnostics, clinical treatments and intervention methods. For information on the House Ear Institute, please call (213) 483-4431 or visit the Web site at www.hei.org.

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