In a mouse study designed to understand how chronic inflammation in sinusitis damages the sense of smell, scientists at Johns Hopkins say they were surprised to learn that the regeneration of olfactory tissue requires some of the same inflammatory processes and chemicals that create injury and loss of smell in the first place.
In a report on their findings, published in Proceedings of the National Academy of Sciences, the researchers say their work adds to scientific understanding of the way olfactory tissue recovers from damage triggered by viruses, toxic chemicals and gases, or allergens.
“The kind of inflammation associated with immune system reactions to fight infection or injury appears to be part of a single system linked to tissue regeneration, so that normal healing of the olfactory system can’t happen without it,” says Andrew Lane, M.D., professor of otolaryngology-head and neck surgery at the Johns Hopkins University School of Medicine. “But more isn’t always better, and continued inflammation will eventually have the opposite effect of killing olfactory neurons and inhibiting their regeneration, resulting in the loss of smell.”
Lane frequently sees patients with chronic sinusitis who’ve lost their sense of smell over time, and this has long been presumed to be due to the permanent destruction of olfactory tissue by inflammation and replacement with scar tissue. However, treating patients with oral steroids that suppress the immune system can bring back the sense of smell temporarily, suggesting that the olfactory tissue is still present in the nose, but that chronic inflammation plays a role in repressing its function. The researchers say that how this might occur has been a mystery.
In the process of testing inflammation’s role in damaging olfactory tissue, researchers gave a chemical, methimazole, to mice that directly damages their olfactory tissue, waited a day, then treated them with a steroid injection. They then biopsied the tissue to measure how many new olfactory basal stem cells were growing and dividing (healing), using BrdU as a marker of replicating DNA. Compared to mice not given the steroids, mice given steroids had 45 percent fewer stem cells proliferating to replace the damaged ones in the tissue, suggesting that suppressing inflammation slowed olfactory stem cell regeneration.