Researchers have made a surprising discovery regarding the relationship between zinc deficiency, the pro-inflammatory cytokine interleukin-13 (IL-13), and lung infections caused by Acinetobacter baumannii. They found that inhibiting IL-13 could prevent deaths from infection in an animal study. This indicates that FDA-approved anti-IL-13 antibodies might offer protection against bacterial pneumonia for patients suffering from zinc deficiency.
A new study published on November 15 in Nature Microbiology highlights that a lack of dietary zinc can increase susceptibility to lung infections from Acinetobacter baumannii, a key contributor to ventilator-associated pneumonia.
A research team from Vanderbilt University Medical Center identified an unexpected connection between interleukin-13 (IL-13) and lung infections caused by A. baumannii. They demonstrated that blocking IL-13 can deter mortality related to these infections in animal models.
The results indicate that anti-IL-13 antibodies, which are already approved by the FDA for human use, could provide protection against bacterial pneumonia in individuals who are zinc deficient.
“To our knowledge, this is the first study demonstrating that blocking IL-13 can prevent death caused by a bacterial infection,” stated Eric Skaar, PhD, MPH, who leads the Vanderbilt Institute for Infection, Immunology and Inflammation. “This finding suggests the potential use of anti-IL-13 treatment for patients with zinc deficiency and A. baumannii pneumonia, marking a step towards personalized therapy.”
Nearly 20% of people worldwide are at risk for zinc deficiency, which can weaken the immune system and significantly raises the risk of pneumonia. The World Health Organization views zinc deficiency as a major contributor to illness and mortality.
Certain groups, especially critically ill patients and the elderly, are more likely to face zinc deficiency and are also at a higher risk for A. baumannii infections. Those in healthcare settings—including patients on ventilators, with catheters, in intensive care, or with extended hospitalizations—are particularly vulnerable. The increasing resistance of A. baumannii to antibiotic treatments poses a severe public health concern, according to Skaar.
To investigate how dietary zinc deficiency affects A. baumannii infections, the researchers created a mouse model to examine the effects of zinc deficiency alongside acute A. baumannii pneumonia. Lauren Palmer, PhD, a former postdoctoral fellow at VUMC and now an assistant professor at the University of Illinois, Chicago, led these studies.
The study revealed that mice lacking zinc had a higher bacterial load from A. baumannii in their lungs, a greater spread of bacteria to the spleen, and increased mortality compared to mice that received adequate zinc. They observed that the zinc-deficient mice produced more IL-13 during infections, and when IL-13 was administered to zinc-sufficient mice, it facilitated the spread of A. baumannii to the spleen. Treatment with anti-IL-13 antibodies helped to protect zinc-deficient mice from death caused by A. baumannii.
This research contributes to a growing body of evidence linking certain nutritional deficiencies to increased IL-13 levels and a “type 2” immune response.
“IL-13 might be a significant risk factor for lung infections related to healthcare settings and opportunistic pathogens, furthering the need to explore IL-13 as a therapeutic target,” Skaar added.
FDA-approved anti-IL-13 antibodies, such as lebrikizumab and tralokinumab, have been extensively studied as treatments for uncontrolled severe asthma. While they didn’t prove effective in that domain, the safety of these therapies was confirmed through clinical trials.
Palmer is the lead and co-corresponding author of the report in Nature Microbiology, alongside Skaar. Other contributors include Zachery Lonergan, PhD, Dziedzom Bansah, Xiaomei Ren, PhD, Lillian Juttukonda, MD, PhD, Christopher Pinelli, DVM, PhD, and Kelli Boyd, DVM, PhD. This research received partial funding from the National Institutes of Health through various grants.
