Chemical warfare agent and biological toxin-induced pulmonary toxicity: could stem cells provide potential therapies?

Abstract

Chemical warfare agents (CWAs) as well as biological toxins present a significant inhalation injury risk to both deployed warfighters and civilian targets of terrorist attacks. Inhalation of many CWAs and biological toxins can induce severe pulmonary toxicity leading to the development of acute lung injury (ALI) as well as acute respiratory distress syndrome (ARDS). The therapeutic options currently used to treat these conditions are very limited and mortality rates remain high. Recent evidence suggests that human stem cells may provide significant therapeutic options for ALI and ARDS in the near future. The threat posed by CWAs and biological toxins for both civilian populations and military personnel is growing, thus understanding the mechanisms of toxicity and potential therapies is critical. This review will outline the pulmonary toxic effects of some of the most common CWAs and biological toxins as well as the potential role of stem cells in treating these types of toxic lung injuries.

Keywords::

• Acute lung injury (ALI)
• acute respiratory distress syndrome (ARDS)
• biological toxin
• chemical warfare agents (CWAs)
• respiratory toxicity
• stem cells

Acknowledgements

The authors thank Dr. Peter Emanuel, Dr. George Famini, and Ms. Kelley Betts for critical review of the manuscript. We thank Ms. Janett Stein and Mr. Patsy D’eramo for library support as well as Ms. April Grimm for administrative support throughout the manuscript preparation process. The authors also thank LTC Greg Saturday, LTC Derron A. Alves, Dr. Fred Sciuto, Dr. Michael W. Perkins, Dr. Benjamin J. Wong, Ms. Tracey Hamilton, and Mr. Dana Anderson from the U.S. Army Medical Research Institute of Chemical Defense for providing the images of CWA-exposed rodent lungs.

Declaration of interest

The work in the corresponding author’s laboratory is funded through the Edgewood Chemical Biological Center and the Department of Homeland Security. D.J.A. is a recipient of a National Research Council Senior Research Associateship. K.L.W. is the recipient of a National Research Council Research Associateship supported and funded through the Defense Threat Reduction Agency. The views expressed in this manuscript are those of the author(s) and do not reflect the official policy of the Department of the Army, Department of Defense, Department of Homeland Security, or the U.S. Government.