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Inflammation boosts drug-induced hearing loss in mice
A class of readily available and low-cost antibiotics called aminoglycosides are commonly used to treat certain types of life-threatening infections, but these medicines damage the ear, causing hearing loss, ringing in the ears (tinnitus), or balance disorders. Results from a new mouse study funded in part by the National Institutes of Health (NIH) show that the widespread, or systemic, inflammation that accompanies severe infections worsens the drug’s toxic effects on hearing, leading to permanent hearing loss. The findings are published online as the cover article in the July 29 issue of Science Translational Medicine and are the topic of a Focus editorial in the journal.
The results suggest that patients treated with aminoglycosides are more likely to develop permanent hearing loss than previously believed. At particular risk for the debilitating impact of hearing loss are newborns and premature babies treated with aminoglycosides. According to the authors, about 80 percent of 600,000 admissions into neonatal intensive care units in the United States are treated with aminoglycosides each year.
Although the toxic effects of aminoglycosides on hearing are well known, how the drugs reach and impact the inner ear is only beginning to be understood. A team of researchers led by Peter S. Steyger, Ph.D., professor of otolaryngology at the Oregon Health and Science University (OHSU), set out to study the role of systemic inflammation.
The scientists used a mouse model of systemic infection and inflammation and gave both sick mice and a group of healthy mice an aminoglycoside. They found that, compared to healthy mice, the sick mice take up more of the drug into the cochlea, a key structure in the inner ear that houses the delicate sensory hair cells critical for hearing. In addition, the mice with widespread inflammation had greater hearing loss across a wider range of frequencies than the healthy mice. Much of the loss was permanent, especially at higher frequencies.
By providing a better understanding of the role and mechanism that inflammation plays on the drugs’ ototoxicity, the study opens doors for scientists to develop new aminoglycosides that won’t permanently hurt hair cells, which are important for balance as well as hearing.
Protecting hair cells during aminoglycoside therapy, limiting treatment with aminoglycoside antibiotics, or substituting other non-ototoxic antibiotic or anti-infective therapies when possible could help hundreds of thousands of patients preserve their hearing. The OHSU research team and others supported by the NIH’s National Institute on Deafness and Other Communication Disorders (NIDCD), which helped fund the new study, are exploring several ways to protect hair cells from damage caused by aminoglycosides and other drugs.
This work was supported by NIDCD (grants R01-DC004555, R01-DC012588, R03-DC011622 and P30-DC005983). Additional support came from the NIH’s National Center for Advancing Translational Sciences, the National Research Foundation of Korea, Seoul National University Bundang Hospital, the Department of Otolaryngology at Oregon Health Sciences University, and the American Otological Society.
In addition to supporting research, the NIDCD provides a wide range of science-based health information on hearing, hearing loss, and deafness.