Substance in iron metabolism displays life-saving potential

In a surprising discovery that someday may lead to new treatments for many inflammatory diseases, University of Utah scientists found that a hormone involved in iron metabolism can save mice from deadly acute inflammation.

 
University of Utah molecular biologists Jerry Kaplan, Ivana De Domenico and Diane Ward have made a surprising discovery that hepicidin -- a hormone that helps regulate iron balance in the body -- can prevent deadly inflammation in mice. Their study raises hope that the substance someday might be used to combat a variety of human inflammatory diseases.
Photo Credit: Curry Koening, the University of Utah

"It's well recognised that the hormone hepcidin helps regulate iron balance. This study shows it has an additional, brand-new, unexpected role in reducing inflammation," says the study's principal author, Jerry Kaplan, a pathology professor and assistant vice president for basic sciences at the University of Utah Health Sciences Center.

The findings by Kaplan and his fellow molecular biologists were scheduled for publication online Monday, June 7 in The Journal of Clinical Investigation and in the print issue dated July 1. The research was funded by the National Institutes of Health.

The study reveals that "hepcidin has an anti-inflammatory effect, reducing the consequences of inflammation," says the study's first author, Ivana De Domenico, an assistant professor of internal medicine.

Coauthor Diane Ward, an associate professor of pathology, adds, "This could mean that hepcidin might be considered as a therapy for a wide range of acute inflammatory conditions such bacterial infections; inflammation from surgery, injury or burns; organ transplantation; and rare cases of inflammation from blood transfusions."
Toxic shock and fever also might be subject to hepcidin treatment, Kaplan says.

"Clinical trials in humans are required to determine if hepcidin is effective at treating human inflammatory conditions - and that will be a few years away," he adds.

Hepcidin rescues cells and mice from fatal inflammation
In the study's key experiments, mice were given one of three substances in doses that cause fatal inflammation: (1) Lipopolysaccharide or LPS, a toxin on the outside of bacteria and recognized as "foreign" by the immune system, inducing inflammation;(2) Poly I:C, which is found in viruses and also provokes inflammation; (3) Turpentine, a solvent used historically to provoke and study inflammation.

Cells called macrophages were cultured in the lab and exposed to LPS. Some cell cultures were pretreated with hepcidin. The untreated cells showed high levels of inflammatory proteins, while the treated cells had lower levels.