Winter 2018

First in the Field

Charles Dinarello and his team cloned interleukin-1, leading to research on how cytokines control the immune response.

By Genevieve Rajewski

In the three decades since Charles Dinarello and his team at Tufts cloned interleukin-1, there have been numerous discoveries about the molecule’s myriad effects in the body—and research on it continues to hold promise for managing difficult-to-treat medical conditions.

One of the first cytokines identified, interleukin-1 (IL-1) is a protein produced by cells that plays a critical role in inflammation, fever, and other ways the body responds to injury and infection. Before interleukin-1 was known by that name, Dinarello set out to learn more about a protein that produced fever in the absence of an infection. He wasn’t alone: Researchers in several fields were all searching for the same protein because of its effects on nearly every tissue and organ system.

Brought to Tufts in 1977 by Sheldon M. Wolff, chair of the Department of Medicine, Dinarello continued the research on IL-1 he had started with Wolff while at the National Institutes of Health. In 1979, he and Wolff published an article positing that the fever molecule Dinarello had isolated and the protein that immunologists were hunting were actually one and the same. But, Dinarello recalled, most scientists argued that it was impossible for a single protein to have so many biological properties. The only way to prove it was to clone the molecule so a pure form was available for controlled study. After three years of research, Dinarello and his team reported the first cloning of IL-1 beta in the Proceedings of the National Academy of Sciences in 1984.

Dinarello’s work on IL-1 “was really the ground floor of a whole new field dedicated to understanding how cytokines control the immune response in people,” said Linden Hu, vice dean of research at the School of Medicine. Close to 70,000 reports have been published on IL-1 since 1984, and Dinarello—now a professor at the University of Colorado School of Medicine and at Radboud University in the Netherlands—has received many awards. Upon accepting the Ernst Jung Prize in 1993, Dinarello endowed the Sheldon M. Wolff Professor in the Department of Medicine at Tufts; he used other prize winnings to create the Interleukin Foundation for Medical Research.

IL-1-blocking meds were some of the first biological products for treating rheumatoid arthritis. Today, blocking IL-1 helps treat gout, as well as periodic fever syndromes and other rare conditions. Cardiologists recently found that using an IL-1-blocking medication to reduce systemic inflammation lowered the rate of recurrent cardiovascular events in people—it also appeared to reduce lung cancer incidence. “So often basic science discoveries do not change the way we care for patients,” said Edouard Vannier, an assistant professor at the School of Medicine. “Some patients already benefit from Charles’ groundbreaking discovery—and the IL-1 saga is far from over.”

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