Interleukin (IL)-23 and -22 Restrict Atherosclerosis by Repressing Pro-Atherogenic Microbiota, Study Shows

Dr. Koltsova

PHILADELPHIA (November 21, 2018) — Research from Fox Chase Cancer Center shows that IL-23 and IL22 cytokines modulate microbiota composition and impact diet-induced atherosclerosis. The paper, by Aliia Fatkhullina, MS, a graduate student at Fox Chase, and Ekaterina Koltsova, MD, PhD, assistant professor in the Blood Cell Development and FunctionProgram at Fox Chase, appears in the journal Immunity.

Cardiovascular disease is the leading cause of death in developed countries. Cancer patients and survivors have at least three-fold higher risk of cardiovascular disease. Inflammation and its mediators, cytokines, are implicated in both cardiovascular disease and cancer. It is generally believed that inhibiting inflammation would be beneficial in reducing the risk of these diseases.

“The expectation in the field was always that inactivation or neutralization of inflammatory cytokines, specifically IL-23, would suppress atherosclerosis progression, however we found that ablation of IL23 or its target IL22 strongly promoted inflammatory cardiovascular disease,” Koltsova said.

IL23 inhibitors have been used to treat various immune-mediated diseases, such as inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, and others. Some human studies of IL-12/IL-23 inhibitors revealed major cardiovascular events, but they were regarded as unexpected side effects without any molecular explanation.

“Our results revealed unexpectedly that the absence of these proteins augments atherosclerosis due to expansion of intestinal bacteria capable of producing pro-atherogenic metabolites,” Koltsova said. “We found that IL23-IL22 cytokine signaling is required to control host-microbial interaction and prevent the emergence of pro-atherogenic metabolites, distantly suppressing diet-induced atherosclerosis via regulation of intestinal homeostasis and inflammation.”

Atherosclerosis is a common chronic lipid-driven inflammatory cardiovascular disease with high morbidity and mortality. These findings provide a mechanistic explanation for adverse cardiovascular events in patients being treated for a range of inflammatory diseases.

This work was supported by Pew Scholar Award; a NCI P30 Cancer Center Grant; NCI R21 CA202396, NIH R56 HL133669, and NIH R01 HL133669; and NIH R01HL103866 This project was supported in whole or in part from Federal funds from the Frederick National Laboratory for Cancer Research, NIH under contract HHSN 261200800001E.

Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence six consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

For more information, call 888-369-2427

Resize Text