Zinc 'taps brakes' in immune response

Scientists determined that a protein lures zinc into key cells that are first-responders against infection.

New research suggests that zinc helps control infections by gently tapping the brakes on the immune response in a way that prevents out-of-control inflammation that can be damaging and even deadly.

Scientists determined in human cell culture and animal studies that a protein lures zinc into key cells that are first-responders against infection. The zinc then interacts with a process that is vital to the fight against infection and by doing so helps balance the immune response.

This study revealed for the first time that zinc homes in on this pathway and helps shut it down, effectively ensuring that the immune response does not spiral out of control. The team led by Ohio State University researchers also found that if there is not enough zinc available at the time of infection, the consequences include excessive inflammation.

In this research, zinc’s activity was studied in the context of sepsis, a devastating systemic response to infection that is a common cause of death in intensive-care unit patients. But scientists say these findings might also help explain why taking zinc tablets at the start of a common cold appears to help stem the effects of the illness.

 “We do believe that to some extent, these findings are going to be applicable to other important areas of disease beyond sepsis,” said Daren Knoell, senior author of the study and a professor of pharmacy and internal medicine at Ohio State. “Without zinc on board to begin with, it could increase vulnerability to infection. But our work is focused on what happens once you get an infection—if you are deficient in zinc you are at a disadvantage because your defense system is amplified, and inappropriately so.

While this study and previous work linking zinc deficiency to inflammation might suggest that supplementation could help very sick ICU patients, it’s still too early to make that leap.

“I think the question is whom to give zinc to, if anybody at all. We predict that not everybody in the ICU with sepsis needs zinc, but I anticipate that a proportion of them would,” Knoell said. “Zinc is a critical element that we get from our diet, but we do not think we can give zinc and fix everything. Usually, if there is zinc deficiency, we would expect to see other nutrient deficiencies, too.”

Zinc deficiency affects about 2 billion people worldwide, including an estimated 40 percent of the elderly in the United States—who are also among the most likely Americans to end up in an ICU.

The research is published in the journal Cell Reports.

Knoell’s lab previously showed that zinc-deficient mice developed overwhelming inflammation in response to sepsis compared to mice on a normal diet. Zinc supplementation improved outcomes in the zinc-deficient mice.

Until now, the beneficial effects of zinc in combating infection have not been fully understood at the molecular level. This is because zinc has numerous complex jobs in the body and interacts with thousands of proteins to sustain human life. Of all the zinc contained in our bodies, only about 10 percent of it is readily accessible to help fight off an infection, said Knoell, also an investigator in Ohio State’s Davis Heart and Lung Research Institute.

“We believe that our findings help to narrow an important gap that has existed in our understanding of how this relatively simple metal helps us defend ourselves from infection,” he said.

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