The mechanism behind zinc's reported ability to help fight off infections may lie in its ability to kick start and shut off immune pathways, say researchers.
The new study suggests that the mineral plays a key role in controlling the body’s response to infections by ‘tapping the breaks’ on immune system pathways in a way that stops them causing a spiral of our-of-control inflammation.
Writing in the journal Cell Reports, the US-based researchers behind the study also found that if there is not enough zinc available at the time of infection, the consequences include excessive inflammation.
Led by Professor Daren Knoell from Ohio State University, USA, the new research reveals for the first time zinc’s role in mediating this pathway and helping shut it down effectively.
"The benefit to health is explicit: Zinc is beneficial because it stops the action of a protein, ultimately preventing excess inflammation," he said.
"We do believe that to some extent, these findings are going to be applicable to other important areas of disease beyond sepsis," explained Knoell.
"Without zinc on board to begin with, it could increase vulnerability to infection,” he suggested. “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 defence system is amplified, and inappropriately so.”
While the primary aim of the study was to explore the link between zinc deficiency and inflammation, Knoell and his team said their findings may also explain why supplementation with zinc at the start of a common cold appears to help stem the effects of the illness.
The research team said while their study and previous research links zinc deficiency to inflammation and may suggest that supplementation could help very sick ICU patients, it is still too early to make that leap.
"I think the question is whom to give zinc to, if anybody at all,” said Knoell. “We predict that not everybody in the ICU with sepsis needs zinc, but I anticipate that a proportion of them would."
"Zinc is a critical element that we get from our diet, but we do not think we can give zinc and fix everything,” he commented. “Usually, if there is zinc deficiency, we would expect to see other nutrient deficiencies, too."
The research team studied the activity of zinc in the context of sepsis – a severe systemic response to infection, that lead to death – using cell culture models.
Knoell's lab previously showed that zinc-deficient mice developed overwhelming inflammation in response to sepsis compared to mice on a normal diet.
In the new study, Knoell and his colleagues focused in on zinc's role in preventing the inflammation that had led to such poor outcomes in the zinc-deficient mice. Using human monocytes (immune cells involved in the first line of defence against infection) the research team examined what happens when the immune response is launched.
They reveal that when a pathogen is recognised, a series of molecules wake up to create a process that activates the immune response but also leads to the expression of a gene that produces a zinc transporter called ZIP8.
This transporter then rapidly moves to the cell's wall, where it can then shuttle zinc from the bloodstream into the cell.
After cell entry, zinc is then directed to and binds to a different protein which then halts any further activity in that process.
The cumulative impact of this feedback loop is that it prevents excessive inflammation, which can be damaging to cells and the body, said the researchers.
"The immune system has to work under very strict balance, and this is a classic example of where more is not always better," Knoell said. "We want a robust inflammatory response, which is part of our natural programming to defend us against a bug. But if that is unchecked, and there is too much inflammation, then it not only attacks the pathogen but can also cause much more collateral damage."
Knoell said that the findings from the study may have therapeutic implications for supplemental zinc “in a strategic manner to help improve some people with certain conditions.”
“But also, could we learn from this so someday we can be more diagnostic about who it is that needs zinc? And if so, what dose and for how long?"
Source: Cell Reports
Published online ahead of print, doi: 10.1016/j.celrep.2013.01.009
“ZIP8 Regulates Host Defense through Zinc-Mediated Inhibition of NF-κB”
Authors: Ming-Jie Liu, Shengying Bao, Marina Gálvez-Peralta, Charlie J. Pyle et al