Collateral Damage

Saving the innocent bystander in the battle against infection

Editor’s Note:  This story, first published in 2004, has been updated.

Melissa Marino, Ph.D.
Published: December, 2004

A macrophage, part of the first line of defense against infection, prepares to engulf an H. pylori bacterium in the stomach lining. Unfortunately, the bacterium will survive this encounter, as well as other inflammatory assaults that end up damaging surrounding tissue. Eventually an ulcer may result.

Illustration by Pat Britten

Humans have been battling inflammation since the dawn of time. Yesterday’s willow tree bark is today’s plethora of pills and tablets. According to IMS Health, a pharmaceutical information and consulting company, more than $17 billion dollars are spent annually in the United States on prescription anti-inflammatory drugs.

The quest for better medicine continues today. Dozens of compounds are moving through the drug-development pipeline to address a growing list of inflammatory conditions.

Meanwhile, scientists are deciphering the interplay of cells, chemical messengers and genes that makes up the language of inflammation. Along with this understanding comes an increased capability to intervene—to treat and ultimately to prevent the disabling, potentially life-threatening and costly consequences of chronic inflammation.

The language of inflammation

Inflammation begins when white blood cells—mast cells, neutrophils, macrophages—residing in tissue respond to the site of an injury or infection. They produce waves of chemicals—called inflammatory “mediators”—that can kill germs and sound the alarm for other populations of inflammatory cells.

Unfortunately, these mediators also “can put tissue on ‘fire,’ and cause ‘collateral damage,’” says Jacek Hawiger M.D., Ph.D., who is leading the search for inflammation-related genes at Vanderbilt University Medical Center.

Inflammation is a complex, multiple signaling phenomenon, but it can be broken down into three basic groups of mediators: reactive oxygen species (ROS) such as hydrogen peroxide and “free radicals” (atoms with unpaired electrons); eicosanoids including the prostaglandins and leukotrienes; and protein messengers called cytokines.