Pharmacy Professor Knoell’s new publication looks at zinc’s role in mitigating sepsis

Daniel Helfand
04/24/2014

A recent publication from the lab of The Ohio State University Charles H. Kimberly Professor of Pharmacy and division chair Daren Knoell suggests the essential nutrient zinc plays a crucial role in fighting sepsis, a life-threatening complication of severe infection where chemical mediators released into the bloodstream in response to infection trigger overwhelming inflammation throughout the body.

The publication entitled, “Zinc Regulates the Acute Phase Response and Serum Amyloid A Production in Response to Sepsis through JAK-STAT3 Signaling” and published in Plos One identified Serum Amyloid A, a protein secreted during the immediate post phase of inflammation, as highly zinc responsive during sepsis. The study also revealed that zinc can regulate the production of Serum Amyloid A to help balance the host defense response through regulation of an important signaling pathway known as the JAK-STAT3 pathway.

“Sepsis spreads quickly and is highly unpredictable,” said Knoell. “There is no known cure for it, and it has a high mortality rate. We hope that our genomics-based approach will facilitate the discovery of much needed biomarkers that will allow clinicians to more accurately diagnose zinc deficiency in sepsis patients and provide new insight into how to better treat those with infection-related complications.”

Sepsis typically occurs in patients that become vulnerable to overwhelming infection due to a weakened immune system. The beginning stage of sepsis is brought on often due to simple infections that can spread rapidly throughout the body. In response to sepsis, the body quickly redistributes zinc into vital organs and cells to protect against infection because zinc is required for important cell functions that provide us with defense.  But, because of the rapid fluctuation in blood zinc levels, it is very difficult to properly determine whether patients are in need of more zinc.

“In patients with sepsis, we do not yet have an accurate method to determine whether or not zinc supplementation would be an effective treatment option,” said Knoell. “Too much zinc can cause additional harm to sepsis patients and not enough zinc can leave patients ill-equipped to fight the complication, so before we can recommend zinc supplementation as a treatment strategy, we need to assure its safety through clinical trials.”

The study used preclinical trials with a model of sepsis in mice that allowed more precise control over the timing of sepsis and body zinc content; however, Knoell believes that this work can spur future research projects in understanding the complex nature of sepsis and hopefully lead to human clinical trials.

“It is well known that the expression of a substantial number of genes change quickly after the development sepsis. Understanding how micronutrients such as zinc impact major gene networks may provide a key for us to better predict how different patients respond and what their needs are,” said Knoell. “Our findings do not suggest everything that happens through JAK-STAT3 in sepsis patients, but it does provide new evidence of the importance of zinc in helping the body mount defense against overwhelming infection.”

This study was funded by the National Institute of Health’s Heart, Lung, and Blood Institute over five years at $250,000 annually.