Zinc Deficiency and Acinetobacter Lung Infections

A research team led by Vanderbilt University Medical Center has uncovered a surprising relationship between the pro-inflammatory cytokine interleukin-13 (IL-13) and A. baumannii lung infections, suggesting that targeting IL-13 could help prevent infection-related death in animal models. This discovery is significant because it highlights the potential of FDA-approved anti-IL-13 antibodies, which are already used in humans, as a therapeutic strategy for bacterial pneumonia, particularly in individuals suffering from zinc deficiency.

“To the best of our knowledge, this is the first time we’ve demonstrated that blocking IL-13 could reduce mortality from bacterial infections,” explained Dr. Eric Skaar, the Ernest W. Goodpasture Professor of Pathology and director of the Vanderbilt Institute for Infection, Immunology and Inflammation. His team’s work could pave the way for personalized treatments for pneumonia patients, especially those with low zinc levels.

Zinc deficiency, affecting approximately 20% of the global population, is a major risk factor for pneumonia due to its impact on immune function. The World Health Organization lists zinc deficiency as a leading cause of disease and death. Vulnerable populations, including the critically ill, elderly, and those in healthcare settings, are particularly susceptible to A. baumannii infections. The bacterium is notably resistant to antibiotics, adding to its threat as a public health concern.

In the study, the researchers induced a zinc-deficient condition in mice and exposed them to A. baumannii pneumonia. The results showed that the zinc-deficient mice had higher bacterial loads in their lungs, more bacterial spread to their spleen, and increased mortality compared to mice with sufficient zinc intake. The team observed that these mice produced elevated levels of IL-13, which facilitated the spread of A. baumannii. When anti-IL-13 antibodies were administered, the zinc-deficient mice showed significantly reduced mortality, suggesting that blocking IL-13 could offer protection against bacterial pneumonia in this group.

The findings align with broader research indicating that nutrient deficiencies can trigger heightened IL-13 production and a type 2 immune response. This points to IL-13 as a key factor in the pathogenesis of healthcare-associated lung infections and strengthens the case for exploring IL-13 inhibitors as a treatment strategy. Anti-IL-13 therapies, such as lebrikizumab and tralokinumab, have already been tested in clinical trials for severe asthma and, while ineffective for that purpose, have been shown to be safe, further supporting their potential application in treating pneumonia.

Commentary by YourDailyFit Columnist Alice Winters:

This breakthrough by Vanderbilt University underscores a compelling intersection between nutrition, immune function, and infection prevention. The finding that IL-13 is a pivotal player in A. baumannii pneumonia in zinc-deficient mice opens new avenues for personalized medicine. Zinc, a crucial micronutrient, plays an indispensable role in immune response, and its deficiency creates a perfect storm for opportunistic infections. The discovery that blocking IL-13 might mitigate the heightened risk of death in these vulnerable individuals presents a promising strategy, especially considering the increasing antibiotic resistance seen in healthcare-associated infections.

However, while the concept of utilizing FDA-approved anti-IL-13 antibodies is an intriguing one, it raises further questions about the broader implications for immune modulation. IL-13 is not merely a villain in this context but also a critical regulator of immune responses, particularly in allergic conditions. Its inhibition, though potentially lifesaving in cases like pneumonia, may have unintended consequences for patients with other immune-related disorders.

The ultimate challenge will be tailoring such treatments to specific populations—those with zinc deficiency and heightened infection risk—while managing the delicate balance of immune system modulation. Given the increasing rates of zinc deficiency globally, especially in vulnerable groups, these findings could help shape more effective, targeted therapies that address both nutritional gaps and immune dysfunction. Moving forward, the research should delve deeper into how IL-13 interacts with other immune pathways and whether long-term inhibition could affect overall immune health.