Daniel Leisman, MD
Daniel Leisman, MD

Daniel Leisman, MD, a resident in the Department of Medicine at Massachusetts General Hospital, is the lead author of a new study in the Proceedings of the National Academy of Sciences (PNAS) titled Angiotensin II Enhances Bacterial Clearance via Myeloid Signaling in a Murine Sepsis Model. Marcia Goldberg, MD, is a collaborating author on the study.

What was the question you set out to answer with this study?

Does angiotensin-II enhance immune function and defense against severe bacterial infections?

Sepsis, a dysregulated immune response to infection, often causes life-threateningly low blood pressure that requires treatment with norepinephrine.

However, norepinephrine is immunosuppressive and may impair bacterial defense. Angiotensin-II, a cardiovascular hormone, is an alternative, recently approved treatment for low blood pressure but whether angiotensin-II impacts immune function in sepsis is unknown.

What are two or three key takeaways?

  1. Angiotensin-II substantially increased bacterial clearance and enhanced immune function without worsening organ injury in a mouse model of sepsis, whereas norepinephrine, the current first line treatment for septic shock, did not.
  2. Angiotensin-II increased immune cells’ ability to engulf bacteria (phagocytosis) and produce bacterial-killing molecules (reactive oxygen species), but only when a bacterial stimulus was also present, suggesting angiotensin-II induces targeted rather than non-specific immune activation.
  3. Angiotensin-II, a hormone commonly inhibited as a treatment for chronic cardiovascular disease, appears to play a key role in how the body defends against severe bacterial infections.

What were your conclusions?

In this study, angiotensin-II acted directly on immune cells to enhance bacterial killing functions, increase bacterial clearance, and modulate systemic inflammatory responses without increasing inflammatory injury.

These immune supporting effects suggest angiotensin-II may have a role in sepsis treatment not just to increase blood pressure, but also as an immunomodulator targeting the immune dysregulation that leads to sepsis.

Paper cited:

Leisman, D. E., Privratsky, J. R., Lehman, J. R., Abraham, M. N., Yaipan, O. Y., Brewer, M. R., Nedeljkovic-Kurepa, A., Capone, C. C., Fernandes, T. D., Griffiths, R., Stein, W. J., Goldberg, M. B., Crowley, S. D., Bellomo, R., Deutschman, C. S., & Taylor, M. D. (2022). Angiotensin II enhances bacterial clearance via myeloid signaling in a murine sepsis model. Proceedings of the National Academy of Sciences of the United States of America, 119(34), e2211370119. https://doi.org/10.1073/pnas.2211370119

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In July 2022, Mass General was named #8 in the U.S. News & World Report list of "America’s Best Hospitals." MGH is a founding member of the Mass General Brigham healthcare system.