Zinc deficiency linked to increased risk of lung infections

Zinc deficiency in the diet promotes lung infection by the bacteria Acinetobacter baumannii -; It is the leading cause of ventilator-related pneumonia, according to a up-to-date study published Nov. 15 in the journal Nature microbiology.

A team of researchers led by Vanderbilt University Medical Center discovered an unexpected link between the pro-inflammatory cytokine interleukin-13 (IL-13) and A. baumannii lung infection and showed that blocking IL-13 prevented infection-related death in patients in an animal model.

The findings suggest that anti-IL-13 antibodies, approved by the FDA for employ in humans, may protect against bacterial pneumonia in patients with zinc deficiency.

To our knowledge, this is the first study showing that neutralization of IL-13 can prevent mortality from bacterial infection. This finding indicates the possibility of using anti-IL-13 therapy in patients with zinc deficiency and A. baumannii pneumonia as a personalized therapy.”

Eric Skaar, PhD, MPH, Ernest W. Goodpasture, professor of pathology and director of the Vanderbilt Institute for Infection, Immunology and Inflammation

Nearly 20% of the world’s population is at risk of zinc deficiency, which can impair immune function and is a major risk factor for pneumonia. The World Health Organization considers zinc deficiency a leading cause of disease and death.

Patients at risk of zinc deficiency, especially critically ill and elderly patients, are also at risk of A. baumannii infection. Patients in healthcare facilities are at the highest risk of infection, especially those who employ ventilators, have devices such as catheters, are in intensive care units, or are in hospital for long periods of time. A. baumannii is becoming increasingly resistant to antimicrobial treatments, making it a critical public health threat, Skaar said.

To investigate whether and how dietary zinc deficiency contributes to the pathogenesis of A. baumannii, researchers established a mouse model of dietary zinc deficiency and acute A. baumannii pneumonia. The research was led by Dr. Lauren Palmer, a former doctoral student at VUMC and now assistant professor of microbiology and immunology at the University of Illinois at Chicago.

The researchers found that zinc-deficient mice had increased A. baumannii bacterial load in the lungs, spread of the bacteria to the spleen, and higher mortality compared to mice consuming adequate amounts of zinc in the diet. They showed that zinc-deficient mice produced more IL-13 during infection and that administering IL-13 to zinc-sufficient mice promoted the spread of A. baumannii to the spleen. Treatment with anti-IL-13 antibodies protected zinc-deficient mice from A. baumannii-induced death.

The findings add to a growing body of research showing that certain nutrient deficiencies are associated with IL-13 production and a “type 2” immune response.

“IL-13 may be an essential risk factor for healthcare-associated and opportunistic lung infections, which further supports research into IL-13 as a treatment target,” Skaar noted.

FDA-approved anti-IL-13 antibodies (lebrikizumab and tralokinumab) have been extensively studied as potential treatments for uncontrolled severe asthma. Although they have not been found to be effective for this indication, clinical trials have demonstrated their safety.

Palmer is Skaar’s first collaborating author with Nature microbiology report. Other authors include Dr. Zachery Lonergan, Dr. Dziedzom Bansah, Dr. Xiaomei Ren, Dr. Lillian Juttukonda, Dr. Christopher Pinelli, DVM, and Dr. Kelli Boyd, DVM. The research was partially financed by the National Institute of Health (grants R01AI101171, R01AI017829, F31AI136255, T32HL094296, F32AI122516, K99HL143441, R00HL143441, P30DK058404).