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The Good, The Bad and the Ugly of Inflammation

Not all Inflammation is the Same

It’s a scourge of modern life, each year gobbling up billions of health care dollars in the United States alone.

When it’s good, it fights off foreign invaders, heals injuries and mops up debris. But when it’s bad, inflammation ignites a long list of disorders: arthritis, asthma, atherosclerosis, blindness, cancer, diabetes and, quite possibly, autism and mental illness.

Fortunately, help is on the way. Vanderbilt University researchers such as Jacek Hawiger, M.D., Ph.D., who has studied the evolving paradigms of inflammation for three decades, are on the front lines of a worldwide scientific campaign to reveal inflammation’s secrets.

Like the Allies during World War II, “we want to intercept the code and change it to our benefit,” says Kasey Vickers, Ph.D., a Vanderbilt pioneer in the fledgling field of microRNA.

Inflammation’s arsenal is packed with powerful weapons.

“Inflammation is the body’s response to microbial, autoimmune, metabolic or physical insults,” including burns and physical trauma, said Hawiger, Distinguished Professor of Medicine and Louise B. McGavock Professor.

White blood cells, including granulocytes and macrophages, are the “first responders” to sites of infection and injury. They emit waves of chemicals that can kill germs outright, and protein messengers called cytokines to carry out a bewilderingly wide array of duties.

When these weapons misfire, however, they can wreak havoc. They can even kill.

TWIN PEAKS

Obesity and its constant companion, type 2 diabetes, are at epidemic proportions in this country. One thing that connects them is inflammation.

Normally, the first responders to the site of injury or infection are white blood cells—including macrophages. They produce waves of chemicals, including cytokines, which can kill germs and sound the alarm for other populations of inflammatory cells.

But fat cells can produce cytokines, too. And as fat tissue grows, it attracts inflammatory cells, particularly macrophages. The burden of obesity also crushes fat cells to death. And that makes the problem worse, as inflammatory cells move in to clean up the debris.

Inflammation also antagonizes the action of insulin, the hormone that stimulates muscle and liver to absorb glucose from the blood. And obesity, insulin resistance and type 2 diabetes, in turn, increase the risk for heart disease.

During the past three years, Vanderbilt researchers Lan Wu, M.D., and Luc Van Kaer, Ph.D., Elizabeth and John Shapiro Professor, have identified two subpopulations of white blood cells that play key roles in obesity-associated inflammation.

“There is still a long way to go,” cautioned Wu, research associate professor of Pathology, Microbiology and Immunology. “You cannot design effective therapies without knowing what comes in, what goes out and ‘what’s cooking’ in the middle.” https://medschool.vanderbilt.edu/vanderbilt-medicine/the-good-the-bad-and-the-ugly-of-inflammation/