Although human population studies have linked air pollution to chronic inflammation of nasal and sinus tissues, direct biological and molecular evidence for cause and effect has been scant. Now, Johns Hopkins researchers report that experiments in mice continually exposed to dirty air have revealed that direct biological effect.

The new findings were published in the American Journal of Respiratory Cell and Molecular Biology.

“In the U.S., regulations have kept a lot of air pollution in check, but in places like New Delhi, Cairo or Beijing, where people heat their houses with wood–burning stoves, and factories release pollutants into the air, our study suggests people are at higher risk of developing chronic sinus problems,” says Murray Ramanathan, MD, associate professor of otolaryngology – head and neck surgery at the Johns Hopkins University School of Medicine.

To see how pollution may directly affect the biology of the upper airways, the researchers exposed 38 eight–week–old male mice to either filtered air or concentrated Baltimore air with particles measuring 2.5 micrometers or less, which excludes most allergens, like dust and pollen. The aerosolized particles, although concentrated, were 30 to 60 percent lower than the average concentrations of particles of a similar size in cities like New Delhi, Cairo and Beijing.

Nineteen mice breathed in filtered air, and 19 breathed polluted air for 6 hours per day, 5 days a week for 16 weeks.

The researchers used water to flush out the noses and sinuses of the mice, and then looked at the inflammatory and other cells in the flushed–out fluid under a microscope. They saw many more white blood cells that signal inflammation, including macrophages, neutrophils and eosinophils, in the mice that breathed in the polluted air compared with those that breathed in filtered air. For example, the mice that breathed in the polluted air had almost four times as many macrophages than mice that breathed filtered air.

The researchers compared specific genes used by immune system cells from the mice that breathed polluted air with the cells of those that breathed filtered air. They found higher levels of messenger RNA – the blueprints of DNA needed to make proteins – in the genes for interleukin 1b, interleukin 13, oncostatin M and eotaxin–1 in the nasal fluid of mice that breathed the polluted air. All those proteins are considered direct biomarkers for inflammation.

The investigators measured the protein levels of interleukin 1b, interleukin 13 and eotaxin–1, which are chemical messengers called cytokines that cause an immune response. They found five to 10 times higher concentrations of the cytokines involved in inflammation in the mice that breathed the polluted air than in those that breathed filtered air. Interleukin 1b is a chemical messenger that promotes inflammation, and both interleukin 13 and eotaxin–1 are chemical messengers that attract eosinophils.

Next, the researchers examined layers of cells along the nasal passages and sinuses under a microscope and found that the surface layer – or epithelium – was, notably, 30 to 40 percent thicker in mice that breathed in polluted air than in those that breathed filtered air. Ramanathan says that a thicker epithelium is another sign of inflammation in humans and other animals.